Cell Membrane Structure and Components PDF

Structure and Components of the Cell Membrane --------------------------------------------- As the fluid mosaic model proposes, the cellular membrane is composed of both lipids and proteins. All membrane structures share a common organization: a phospholipid bilayer with embedded proteins.^\[5\]^ The membrane proteins are responsible for carrying out several essential functions in organisms. Also, other than proteins and lipids, carbohydrates are a vital component of the structure. They are only present on the outer side of the cell membrane, attached by covalent bonds to some lipids and proteins. Moreover, one must know that the primary physical force that organizes the lipid bilayer is "hydrophobic force."^\[5\]^ ### Membrane Lipids All membrane lipids are amphipathic -- have both hydrophilic and hydrophobic ends. They constitute around 50% of the mass of most cell membranes. The proportion of lipids differs depending on the type of cell membrane. For example, the plasma membrane is composed of approximately 50% lipid and 50% proteins. Whereas the inner membrane of the mitochondria is 25% lipid and 75% protein.^\[5\]^ Lipid bilayer showing the hydrophobic head and hydrophilic tail Image: An illustration of lipid bilayer showing the hydrophobic head (pink) facing an aqueous environment and the hydrophilic tail facing inwards, away from the water. Source: Watson H. (2015). Biological membranes.^\[6\]^ Similarly, the composition of lipids in the biological membrane also differs depending on the organisms. For example, the plasma membrane of E. *coli *consists predominantly of phosphatidylethanolamine (constituting 80% of total membrane lipid). In contrast, the mammalian plasma membrane comprises four different phospholipids (making up 50-60% of total membrane lipids), glycolipids, and cholesterol (which both make up the other 40%). Below is a brief on all the three classes of lipids: Phospholipids, glycolipids, and sterols.^\[6\]^ #### **1. Phospholipids** It consists of four components: alcohol (glycerol and sphingosine), fatty acids, phosphate, and an alcohol attached phosphate.^\[6\]^ The simplest phospholipid is phosphatidic acid, in which two fatty acid residues are esterified to the OH groups at carbon atoms 1 and 2 of glycerol-3-phosphate. Two main types of phospholipids include glycerophospholipids and sphingophospholipids. - **Glycerophospholipid:** These are phospholipids containing glycerols. Phosphatidylcholine is the most commonly found glycerophospholipid in the membrane. It has a choline molecule attached to the phosphate ring. Cells make many other types of glycerophospholipids by combining different fatty acids and head groups. Other examples are phosphatidic acid, phosphatidylethanolamine, and phosphatidylserine.^\[6\]^ - **Sphingophospholipid:** These molecules contain sphingosine rather than glycerols. Sphingosine is a long acyl chain with an amino group (NH2), two hydroxyl groups (OH), and a phosphocholine group (attached to the terminal hydroxyl group) at one end, forming the hydrophilic head of the sphingophospholipid's structure. The hydrophobic fatty acid tail (attached to the amino group) forms the other end of the structure.^\[6\]^ - Phosphatidylcholine, phosphatidylserine, phosphatidylethanolamine, and sphingomyelin are the **four major phospholipids, **constituting more than half the mass of lipids in most mammalian cell membranes.^\[6\]^ #### **2. Glycolipids** - The structure of glycolipids contains either glycerol or sphingosine and has sugar in place of phosphate head --- different from that seen in sphingolipids.^\[6\]^ - In eukaryotic plasma membranes, it only makes up 5% of the lipid molecules in the outer monolayer.^\[7\]^ - The most complex glycolipid is ganglioside which contains oligosaccharides with one or more sialic acid moieties.^\[7\]^ #### **3. Sterols** - Cholesterol is the principal sterol present in plasma membranes. They account for about 20% of the lipids in animal cell plasma membranes.^\[7\]^ - The structure of cholesterol consists of a hydroxyl group (which is the hydrophilic 'head' region), a four-ring steroid structure, and a short hydrocarbon side chain.^\[7\]^ - Plants contain sterols like stigmasterol and sitosterol in their cell membrane. - In bacterial cell membranes, sterols are absent. ![Membrane lipids atructures](media/image2.png) Image: An schematic representation of the structures of (a) Phosphatidylcholine, a glycerophospholipid; (b) Glycolipid; and (c) Sterol. Source: Watson H. (2015). Biological membranes.^\[6\]^ ### Membrane Proteins Membrane proteins are an integral and dynamic part of the cell membrane. They account for at least half of the mass of most membranes. Their presence is essential in the membrane for signaling, communication, and several other life processes of organisms. There are two categories of membrane proteins based on their association with the plasma membrane:^\[8\]^ #### **1. Intrinsic Membrane Protein** These are proteins that are completely or partially embedded within the plasma membrane. They are also known as integral membrane proteins. Most of these proteins contain hydrophobic side chains that interact with the fatty acyl group of membrane phospholipids and facilitate anchoring the proteins to the membrane.^\[8\]^ One classic example of the integral membrane protein is single pass or multipass transmembrane proteins. These proteins contain one or more membrane-spanning regions (α-helices or multiple β-strands) and regions extending in the aqueous medium on each side of the bilayer.^\[8\]^ An example of single-pass transmembrane protein is RBC glycophorins, and that of multipass transmembrane proteins is band-3 proteins or chloride-bicarbonate exchange proteins of RBCs.^\[8\]^ The integrity of the transmembrane proteins with the phospholipid bilayer makes it experimentally challenging to isolate them by simple extraction procedures. #### **2. Extrinsic Membrane Protein** Extrinsic membrane proteins don't span the hydrophobic core of the membrane.^\[8\]^ These proteins are either indirectly bound to the membrane through interaction with integral membrane protein or directly bound to the lipid polar head group. They are bound to membranes mainly by electrostatic and hydrogen bond interactions. These proteins are also known as peripheral membrane proteins.^\[8\]^ The extrinsic membrane proteins are localized to the cytosolic face of the membrane and play an essential role in signal transduction. These proteins include cytoskeletal proteins spectrin and actin of RBCs, and protein kinase C enzyme.^\[8\]^ The extrinsic membrane proteins can be easily isolated either by using solutions of very high or low ionic strengths, solutions of extreme pH or by gentle extraction.^\[8\]^ ### Membrane Carbohydrates Carbohydrates are the third major component of plasma membranes. They are attached to the outer side of the membrane while being linked to proteins (forming glycoprotein) or lipids (forming glycolipid).^\[9\]^ They also occur as polysaccharide chains of an integral membrane, called proteoglycans. These carbohydrates are composed of 2-60 monosaccharide units (that can be either straight or branched) and coat the surface of all eukaryotic cells.^\[9\]^ - **Glycoproteins:** It's composed of protein attached with one or more oligosaccharides. They participate in a wide range of cellular phenomena, including cell recognition and cell surface antigenicity.^\[9\]^ - **Glycolipids:** It's a carbohydrate covalently linked to membrane lipids. They are involved in maintaining cell stability and facilitating cellular recognition.^\[9\]^ - **Proteoglycans:** They consist of long polysaccharide chains linked covalently to a protein core and are found outside the cell as part of the extracellular matrix. In simple words, they are proteins that are heavily glycosylated.^\[9\]^ Their major functions are derived from the physicochemical characteristics of the glycosaminoglycan component of the molecule, which provides hydration and swelling pressure to the tissue enabling it to withstand compressional forces.^\[9\]^ Properties of the Lipid Bilayer ------------------------------- The lipid bilayer structure can be observed by using electron microscopy, x-ray diffraction, and freeze-fracture electron microscopy techniques. The techniques helped reveal the details of the membrane's organization and its properties attributed to the lipid molecules. Three such properties of the cell membrane include asymmetry, fluidity, formation of lipid rafts. ### 1. Asymmetry in the plasma membrane The asymmetry of the plasma membrane denotes the difference in the composition of lipids in the two monolayers of a lipid bilayer. For example, in red blood cells, almost all lipid molecules with choline---(CH3)3N+CH2CH2OH---in their head group (phosphatidylcholine and sphingomyelin) are in the outer monolayer. While almost all phospholipid molecules containing a terminal primary amino group (phosphatidylethanolamine and phosphatidylserine) are in the inner monolayer.^\[10\]^ The asymmetric lipid distribution between the two lipid monolayers also causes a charge difference between them. At neutral pH, phosphatidylserine is negatively charged, making the cytosol side of the layer more negative than the outer side.^\[10\]^ The other lipids, phosphatidylethanolamine, phosphatidylcholine, and sphingomyelin, are neutral, thus, carry no charges. ### 2. The fluidity of the plasma membrane The term "fluid" in the fluid mosaic model denotes the motion of the lipids in the membrane or its fluid behavior. The membrane lipid molecules possess both rotational and lateral motion. The movement depends on three factors: temperature, lipid composition, and cholesterol.^\[10\]^ - **Temperature:** At higher temperatures, membranes are more fluid, and at a lower temperature, they act as a viscous substance. - **Cholesterol:** In eukaryotes, higher cholesterol concentration decreases the fluidity of the membrane. But, this property of cholesterol also depends on the temperature. For example, at higher temperatures, the membrane is less fluid than at lower temperatures.^\[10\]^ - **Lipid Composition:** Shorter chain length and higher unsaturation levels in fatty acids in the membrane increase the membrane's fluidity. Here's more on the[ factors affecting membrane permeability and fluidity.](https://wordpress-1207589-4279038.cloudwaysapps.com/factors-affecting-cell-membrane-permeability-and-fluidity/) Effect of unsaturated fatty acids on membrane fluidity **Image:** An illustration of the effect of unsaturated fatty acids on membrane fluidity. The saturated fatty acids tightly pack the lipids in the membrane, thus, decreasing their fluidity.^\[10\]^ Source: [Molecular Biology of the Cell. 4th edition](https://www.ncbi.nlm.nih.gov/books/NBK26871/). ### 3. Formation of lipid rafts in the plasma membrane The lipid molecules in the membrane are randomly organized and connected to the neighboring fatty acids through Van der Waals attractive forces.^\[10\]^ For some lipid molecules like sphingophospholipids having long and saturated fatty hydrocarbon chains, the attractive force is so strong that it links the adjacent molecules transiently in small microdomains. These microdomains are called lipid rafts.^\[10\]^ Lipid rafts are approx 70 nm in diameter and rich in sphingolipids and cholesterol. They are of two types: non-caveolar and caveolae (contain caveolin proteins). These lipids rafts are involved in signal transduction, endocytosis, and cholesterol trafficking in cells.^\[10\]^ ![Lipid rafts diagram](media/image4.png) Figure: A diagrammatic representation of the lipid rafts.^\[7\]^ Source: Alberts et al. (2015) Pg. 537 Functions of Biological Membranes --------------------------------- 1. The asymmetry in the plasma membrane helps to distinguish between live and dead cells. Phosphatidylserine, usually confined to the cytosolic side of the plasma membrane lipid bilayer, rapidly translocates to the extracellular monolayer when animal cells undergo programmed cell death or apoptosis. The presence of phosphatidylserine on the cell surface serves as a signal to induce neighboring cells, such as macrophages to phagocytose the dead cell and digest it.^\[10\]^ 2. The glycocalyx coat formation on the cell surface protects it from damage or harm and mediates cell-cell adhesion events.^\[10\]^ 3. The peripheral proteins that form an extracellular matrix on the cell surface have an essential role in cell recognition. 4. The plasma membrane protects the cell from the outer environment and maintains the favorable environment inside the cell. 5. The biological membrane has an essential role in the transport of molecules performed by the membrane proteins. And based on these functions, membrane proteins are also classified into channel protein and carrier protein. - **Channel Protein:** These proteins transport the molecules down the gradient -- that is, passive transport. The channels can be gated or non-gated based on the signal required to initiate the functional response. - **Carrier Protein:** These proteins can be uniport, symport, or antiport. Uniport is the transfer of molecules on only one side of the membrane, symport is the simultaneous transfer of two molecules in the same direction, and antiport is the simultaneous transfer of two molecules in opposite directions. The symport and antiport transportations are together known as co-transport. The transport of molecules through carrier proteins can be done via [active transport](https://wordpress-1207589-4279038.cloudwaysapps.com/active-transport-definition-types-and-examples/) or [passive transport](https://wordpress-1207589-4279038.cloudwaysapps.com/passive-transport/) processes. Co-transport types Image: An illustration of types of co-transport and their examples.^\[6\]^ Source: Watson H. (2015). Biological membranes. Conclusion ---------- Biological membranes are the boundary of cells that protect them from the external environment and perform essential functions required for living organisms. The properties of the cell membranes are similarly/equally shared in both prokaryotic and eukaryotic organisms. The bilayer of the membrane is composed of three major biomolecules: lipids, proteins, and carbohydrates. Further, the advancement in biophysical techniques and availability of substantial computational power is expanding our understanding of the lipid bilayers and providing critical insights into their structures and functions.^\[6\]^ Scientists are currently working towards understanding the properties, functions, and mechanisms of the membrane proteins, which they think might be the key to fighting deadly diseases.^\[6\]^ References: ----------- 1. Biological Membrane. Retrieved from . 2. History of Cell Membrane Theory. Retrieved from . 3. Membrane Models. Retrieved from . 4. Cell Membrane. Retrieved from . 5. Cooper, G. M., & Hausman, R. E. (2007). The cell: A molecular approach. 4th ed. Washington, D.C.: Sunderland, Mass.: ASM Press. 6. Watson H. (2015). Biological membranes. Essays in biochemistry, 59, 43--69. . 7. Alberts, B., Johnson, A., Lewis, J., Raff, M., Roberts, K., & Walter, P. (2015). Molecular biology of the cell, 6th edition. New York: Garland Science. 8. Lodish H, Berk A, Zipursky SL, et al. Molecular Cell Biology. 4th edition. New York: W. H. Freeman; 2000. Section 3.4, Membrane Proteins. Available from: . 9. Aryal Sagar (2021). Membrane Carbohydrates. Retrieved from . 10. Alberts B, Johnson A, Lewis J, et al. Molecular Biology of the Cell. 4th edition. New York: Garland Science; 2002. The Lipid Bilayer. Available from: Course Name- Cell Biology Paper code: MZO-(503) Unit: Structure and Functions of the Cell Membranes Dr. Mukta Joshi Department of Zoology Uttarakhand Open University Haldwani Cell Membrane Introduction: The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological biological membrane membrane that separates the that separates the interior interior of all cells from the outside environment (the extracellular space) which protects the cell from its environment. The cell membrane consists of a lipid bilayer, including cholesterols (a lipid component) that sit between phospholipids to maintain their fluidity at various temperatures. The membrane also contains membrane proteins, including integral proteins that go across the membrane serving as membrane transporters, and peripheral proteins that loosely attach to the outer (peripheral) side of the cell membrane, acting as enzymes shaping the cell. The cell membrane controls the movement of substances in and out of cells and organelles. In this way, it is selectively permeable to ions and organic molecules. In addition, cell membranes are involved in a variety of cellular processes such as cell adhesion, ion conductivity and cell signalling and serve as the attachment surface for several extracellular structures, including the cell wall, the carbohydrate layer called the glycocaly and the intracellular network of protein fibers called the cytoskeleton. Chemical composition The cell membrane is composed mainly of protein, lipid, and a small percentage of oligosaccharides that may be attached to either the lipids(glycolipids) or the proteins (glycoprotens). There is a wide variation in the lipid-protein ratio between different cell membranes. ¬ Lipid Fraction of Cell Membranes- The cell membrane contains about 20 to 79% of lipid. The main lipid constituents of cell membrane are phospholipids, cholesterol and galactolipids; their proportions varies in different cell membranes. The phospholipids components of cell membrane are of two kindsi) neutral phospholipids and ii) acidic phospholipids Neutral phospholipids such as phosphatidylcholine, phosphatidylethanolamine and sphingomyelin have no net charge at neutral pH and they tend to pack tightly in the bilayer. Acidic phospholipids such as phosphatidylinositol, phosphatidylserne, cardiolipin, phosphatidylgcerol, sulpholipds are negatively charged and in the membrane are associated principally with proteins by way of lipid-protein interractions. ¬ Carbohydrate Fraction of Cell Membrane- 1962 Bell has suggested the cell membrane of carbohydrates in the plasma membrane. The most common oligosaccharides of cell membrane of mammalian erythrocytes and liver cells are hexose, hexosamine hexosamine, fucose and sialic acid. Salic acid is sensitive to neuraminidase and is attached to proteins by N-acetylgactosamine on the outer surface of the membrane A small amount of sialic acid exists in the form of gangliosides (i.e., glycolipids) in the plasma membrane of liver cells They play an important role, not only in the mechanical structure of the membrane, but also as carriers or channels, serving for transport. ¬ Protein Fraction of Cell Membranes Proteins represent main and one of the most significant fractions of cell membranes. They play an important role, not only in the mechanical structure of the membrane, but also as carriers or channels, serving for transport, they may also be involved in regulatory or ligand-recognition properties. Besides the structural proteins, there occur enzymatic proteins, and also the antigens and various kinds of receptor molecules, in the plasma membrane. ¬ Enzymes of Cell Membrane In any cell in which active transport occurs, it is likely that enzyme occur in the surface of the cell. The structural protein of a cell membrane is enzymatic protein (Chambers and Chambers,1961). About 30 enzyme have been reported from the isolated cell membranes. Most constantly found are 5- nucleotidaes, Mg2+ ATPase, Na+-K+activated-Mg+Atpase, alkaline phosphatase, adenyl cyclase, acid phosphomonoesterase and RNAse. The enzyme Na+-K+ activated-Mg+ATPase is one of the most important enzyme of plasma membrane because of its role in ion transfer across the plasma membrane. Structure of the Cell Membrane Phospholipids are a main component of the cell membrane. These are lipid molecules made up of a phosphate group head and two fatty acid tails. The properties of phospholipid molecules allow them to spontaneously form a double-layered membrane. When in water or an aqueous solution, which includes the inside of the body, the hydrophilic heads of phospholipids will orient themselves to be on the outside, while the hydrophobic tails will be on the inside. The technical term for this double layer of phospholipids that forms the cell membrane is a phospholipid bilayer. Eukaryotic cells, which make up the bodies of all organisms except for bacteria and archaea, also have a nucleus that is surrounded by a phospholipid bilayer membrane. In addition, the cell membrane contains glycolipids and sterols. One important sterol is cholesterol, which regulates the fluidity of the cell membrane in animal cells. When there is less cholesterol, membranes become more fluid, but also more permeable to molecules. The amount of cholesterol in the membrane helps maintain its permeability so that the right amount of molecules can enter the cell at a time, not too many or too few. The cell membrane also contains many different proteins. Proteins make up about half of the cell membrane. Many of these proteins are transmembrane proteins, which are embedded in the membrane but stick out on both sides. Some of these proteins are receptors which bind to signal molecules, while others are ion channels which are the only means of allowing ions into or out of the cell. Scientists use the fluid mosaic model to describe the structure of the cell membrane. Models of Plasma Membrane Danielli and Davson Model: In 1935 , Danielli and Davson studied triglyceride lipid bilayers over a water surface In their model, Danielli and Davson proposed that the plasma membrane consists of two layers of lipid (phospholipid) molecules. They found that they arranged themselves with the polar heads facing outward It always formed droplets (oil in water) and the surface tension was much higher than that of cells Robertson's Model: In 1965, Robertson noted the structure of membranes seen in the electron micrographs He saw no spaces for pores in the electron micrographs He hypothesized that the railroad track appearance came from the binding of osmium tetroxide to proteins and polar groups of lipids Proposed unit membrane hypothesis Fluid Mosaic Model: According to S.J.Singer and G.L.Nicolson 1972, the biological membranes can be considered as a two dimensional liquid where all lipid and protein molecules diffuse more or less freely. Singer studied phospholipid bilayers and found that they can form a flattened surface on water, with no requirement for a protein coat. It occur in form of globular protein. Widely accepted modal. Fluid Mosaic Model Function of the Cell Membrane The cell membrane is the cell's flexible outer limiting barrier that separates the cell's internal environment from the external (extracellular) environment. It present in prokaryotes and eukaryotes. Oxygen, which cells need in order to carry out metabolic functions such as cellular respiration, and carbon dioxide, a byproduct of these functions, can easily enter and exit through the membrane. Water can also freely cross the membrane, although it does so at a slower rate. However, highly charged molecules, like ions, cannot directly pass through, nor can large macromolecules like carbohydrates or amino acids. During exocytosis, vesicles come to the surface of the cell membrane, merge with it, and release their contents to the outside of the cell. Exocytosis removes the cell's waste products-- parts of molecules that are not used by the cell. The cell membrane also plays a role in cell signaling and communication. Receptor proteins on the cell membrane can bind to molecules of substances produced by other areas of the body, such as hormones. Cell Membrane: Functions When a molecule binds to its target receptor on the membrane, it initiates a signal transduction pathway inside the cell that transmits the signal to the appropriate molecules. Then, the cell can perform the action specified by the signal molecule, such as making or stopping production of a certain protein. Cell membrane provide a binding site for enzyme. Thank you [Biochemical composition and functions of the cell membrane **wikipedia**](https://www.google.com/search?sca_esv=5ac10ce223656a07&sca_upv=1&sxsrf=ADLYWII-dEDsmebDhilSioiJ4-g1zE029Q:1727290143029&q=Biochemical+composition+and+functions+of+the+cell+membrane+wikipedia&sa=X&ved=2ahUKEwiAtJib4d6IAxVP_rsIHZLMDG8Q1QJ6BAhQEAE) [Biochemical composition and functions of the cell membrane **pdf**](https://www.google.com/search?sca_esv=5ac10ce223656a07&sca_upv=1&sxsrf=ADLYWII-dEDsmebDhilSioiJ4-g1zE029Q:1727290143029&q=Biochemical+composition+and+functions+of+the+cell+membrane+pdf&sa=X&ved=2ahUKEwiAtJib4d6IAxVP_rsIHZLMDG8Q1QJ6BAhPEAE) [Biochemical composition and functions of the cell membrane **notes**](https://www.google.com/search?sca_esv=5ac10ce223656a07&sca_upv=1&sxsrf=ADLYWII-dEDsmebDhilSioiJ4-g1zE029Q:1727290143029&q=Biochemical+composition+and+functions+of+the+cell+membrane+notes&sa=X&ved=2ahUKEwiAtJib4d6IAxVP_rsIHZLMDG8Q1QJ6BAhKEAE) [Cell membrane **function**](https://www.google.com/search?sca_esv=5ac10ce223656a07&sca_upv=1&sxsrf=ADLYWII-dEDsmebDhilSioiJ4-g1zE029Q:1727290143029&q=Cell+membrane+function&sa=X&ved=2ahUKEwiAtJib4d6IAxVP_rsIHZLMDG8Q1QJ6BAhNEAE) [Cell **wall**](https://www.google.com/search?sca_esv=5ac10ce223656a07&sca_upv=1&sxsrf=ADLYWII-dEDsmebDhilSioiJ4-g1zE029Q:1727290143029&q=Cell+wall&sa=X&ved=2ahUKEwiAtJib4d6IAxVP_rsIHZLMDG8Q1QJ6BAhJEAE) [Cell membrane **structure** and **function**](https://www.google.com/search?sca_esv=5ac10ce223656a07&sca_upv=1&sxsrf=ADLYWII-dEDsmebDhilSioiJ4-g1zE029Q:1727290143029&q=Cell+membrane+structure+and+function&sa=X&ved=2ahUKEwiAtJib4d6IAxVP_rsIHZLMDG8Q1QJ6BAhMEAE) [**5** functions of cell membrane](https://www.google.com/search?sca_esv=5ac10ce223656a07&sca_upv=1&sxsrf=ADLYWII-dEDsmebDhilSioiJ4-g1zE029Q:1727290143029&q=5+functions+of+cell+membrane&sa=X&ved=2ahUKEwiAtJib4d6IAxVP_rsIHZLMDG8Q1QJ6BAhOEAE) [Cell membrane **diagram**](https://www.google.com/search?sca_esv=5ac10ce223656a07&sca_upv=1&sxsrf=ADLYWII-dEDsmebDhilSioiJ4-g1zE029Q:1727290143029&q=Cell+membrane+diagram&sa=X&ved=2ahUKEwiAtJib4d6IAxVP_rsIHZLMDG8Q1QJ6BAhLEAE) Page navigation =============== Cell Membranes ============== Cell membranes protect and organize cells. All cells have an outer plasma membrane that regulates not only what enters the cell, but also how much of any given substance comes in. Unlike prokaryotes, eukaryotic cells also possess internal membranes that encase their [organelles](https://www.nature.com/scitable/topicpage/the-origin-of-plastids-14125758) and control the exchange of essential cell components. Both types of membranes have a specialized structure that facilitates their gatekeeping function. **What Are Cellular Membranes Made Of?** ---------------------------------------- With few exceptions, cellular membranes --- including plasma membranes and internal membranes --- are made of **glycerophospholipids**, molecules composed of glycerol, a phosphate group, and two fatty acid chains. **Glycerol** is a three-carbon molecule that functions as the backbone of these membrane lipids. Within an individual glycerophospholipid, fatty acids are attached to the first and second carbons, and the phosphate group is attached to the third carbon of the glycerol backbone. Variable head groups are attached to the phosphate. Space-filling models of these molecules reveal their cylindrical shape, a geometry that allows glycerophospholipids to align side-by-side to form broad sheets (Figure 1). ![A schematic shows a glycerophospholipid molecule in four different ways. Panel A shows 30 phospholipids arranged in a bilayer with 15 phospholipid molecules on each side of the bilayer. Panel B uses a sphere and lines to show the basic structure of an individual glycerophospholipid molecule. Panel C uses a ball-and-stick model to show the molecular structure of a glycerophospholipid molecule with each of its four distinct structural elements shaded in a different color. Panel D shows the specific atoms that make up the four structural elements of the phospholipid shown in panel C.](media/image6.jpeg) **Figure 1: The lipid bilayer and the structure and composition of a glycerophospholipid molecule** \(A) The plasma membrane of a cell is a bilayer of glycerophospholipid molecules. (B) A single glycerophospholipid molecule is composed of two major regions: a hydrophilic head (green) and hydrophobic tails (purple). (C) The subregions of a glycerophospholipid molecule; phosphatidylcholine is shown as an example. The hydrophilic head is composed of a choline structure (blue) and a phosphate (orange). This head is connected to a glycerol (green) with two hydrophobic tails (purple) called fatty acids. (D) This view shows the specific atoms within the various subregions of the phosphatidylcholine molecule. Note that a double bond between two of the carbon atoms in one of the hydrocarbon (fatty acid) tails causes a slight kink on this molecule, so it appears bent. **© 2010 [Nature Education](http://www.nature.com/nature_education) All rights reserved. **View Terms of Use [**Figure Detail**](javascript:void(0)) Glycerophospholipids are by far the most abundant lipids in cell membranes. Like all lipids, they are insoluble in water, but their unique geometry causes them to aggregate into [bilayers](https://www.nature.com/scitable/topicpage/discovering-the-lipid-bilayer-14225438) without any energy input. This is because they are two-faced molecules, with hydrophilic (water-loving) phosphate heads and hydrophobic (water-fearing) hydrocarbon tails of fatty acids. In water, these molecules spontaneously align --- with their heads facing outward and their tails lining up in the bilayer\'s interior. Thus, the hydrophilic heads of the glycerophospholipids in a cell\'s plasma membrane face both the water-based cytoplasm and the exterior of the cell. Altogether, lipids account for about half the mass of cell membranes. Cholesterol molecules, although less abundant than glycerophospholipids, account for about 20 percent of the lipids in animal cell plasma membranes. However, cholesterol is not present in bacterial membranes or mitochondrial membranes. Also, cholesterol helps regulate the stiffness of membranes, while other less prominent lipids play roles in cell signaling and cell recognition. ![A schematic shows a cross-section of a cell membrane, which is made up of phospholipids that form a bilayer. Each phospholipid molecule is shown as a round phospholipid head with two squiggly fatty acid tails extending from it. A sheet-like layer of phospholipid molecules is positioned opposite and above a second sheet-like layer of phospholipid molecules. Fatty acid tails from the top and bottom layers extend into the center space so that the tails from the top layer meet the tails from the bottom layer; their phospholipid heads form the top and bottom surface of the bilayer. Six proteins of various shapes and sizes span the width of the membrane. Some form channels within the phospholipid bilayer.](media/image8.jpeg) **Figure 2: The glycerophospholipid bilayer with embedded transmembrane proteins** **© 2010 [Nature Education](http://www.nature.com/nature_education) All rights reserved. **View Terms of Use In addition to lipids, membranes are loaded with proteins. In fact, proteins account for roughly half the mass of most cellular membranes. Many of these proteins are embedded into the membrane and stick out on both sides; these are called **transmembrane proteins**. The portions of these proteins that are nested amid the hydrocarbon tails have hydrophobic surface characteristics, and the parts that stick out are hydrophilic (Figure 2). At physiological temperatures, cell membranes are fluid; at cooler temperatures, they become gel-like. Scientists who model membrane structure and dynamics describe the membrane as a fluid mosaic in which transmembrane proteins can move laterally in the lipid bilayer. Therefore, the collection of lipids and proteins that make up a cellular membrane relies on natural biophysical properties to form and function. In living cells, however, many proteins are not free to move. They are often anchored in place within the membrane by tethers to proteins outside the cell, cytoskeletal elements inside the cell, or both. **What Do Membranes Do?** ------------------------- Cell membranes serve as barriers and gatekeepers. They are semi-permeable, which means that some molecules can diffuse across the lipid bilayer but others cannot. Small hydrophobic molecules and gases like oxygen and carbon dioxide cross membranes rapidly. Small polar molecules, such as water and ethanol, can also pass through membranes, but they do so more slowly. On the other hand, cell membranes restrict diffusion of highly charged molecules, such as ions, and large molecules, such as sugars and amino acids. The passage of these molecules relies on specific transport proteins embedded in the membrane. ![A schematic shows a cross-section through a round cell with six different transport protein complexes arranged across different regions of the cell membrane. Each protein complex acts as a pore and is shown shuttling molecules either from the outside of the cell to the cell\'s interior, from the cell\'s interior to the outside of the cell, or in both directions. Various molecules of different colors are shown inside and outside of the cell. Small spherical molecules are labeled \\\"ions,\\\" and larger circular molecules are labeled \\\"amino acids.\\\" Glucose is shown as a ball-and-stick model. Different transport proteins are specialized to transport particular molecules. A blue protein complex is shown only transporting blue ions out of the cell, and a red protein complex is shown only transporting red ions into the cell. A purple protein complex is shown only transporting amino acids of different colors into the cell, and a green protein complex labeled \\\"glucose transporter\\\" is shown only transporting glucose molecules into and out of the cell.](media/image9.jpeg) **Figure 3: Selective transport** Specialized proteins in the cell membrane regulate the concentration of specific molecules inside the cell. **© 2010 [Nature Education](http://www.nature.com/nature_education) All rights reserved. **View Terms of Use Membrane transport proteins are specific and selective for the molecules they move, and they often use energy to catalyze passage. Also, these proteins transport some nutrients against the concentration gradient, which requires additional energy. The ability to maintain concentration gradients and sometimes move materials against them is vital to cell health and maintenance. Thanks to membrane barriers and transport proteins, the cell can accumulate nutrients in higher concentrations than exist in the environment and, conversely, dispose of waste products (Figure 3). Other transmembrane proteins have communication-related jobs. These proteins bind signals, such as hormones or immune mediators, to their extracellular portions. Binding causes a conformational change in the protein that transmits a signal to intracellular messenger molecules. Like transport proteins, receptor proteins are specific and selective for the molecules they bind (Figure 4). ![A schematic diagram shows a cross section of four plasma membrane proteins performing different functions. The four proteins include a transporter, a receptor, an enzyme, and an anchor.](media/image10.jpeg) **Figure 4: Examples of the action of transmembrane proteins** Transporters carry a molecule (such as glucose) from one side of the plasma membrane to the other. Receptors can bind an extracellular molecule (triangle), and this activates an intracellular process. Enzymes in the membrane can do the same thing they do in the cytoplasm of a cell: transform a molecule into another form. Anchor proteins can physically link intracellular structures with extracellular structures. **© 2010 [Nature Education](http://www.nature.com/nature_education) All rights reserved. **View Terms of Use [**Figure Detail**](javascript:void(0)) **Peripheral membrane proteins** are associated with the membrane but are not inserted into the bilayer. Rather, they are usually bound to other proteins in the membrane. Some peripheral proteins form a filamentous network just under the membrane that provides attachment sites for transmembrane proteins. Other peripheral proteins are secreted by the cell and form an extracellular matrix that functions in cell recognition. **How Diverse Are Cell Membranes?** ----------------------------------- In contrast to prokaryotes, eukaryotic cells have not only a plasma membrane that encases the entire cell, but also intracellular membranes that surround various organelles. In such cells, the plasma membrane is part of an extensive **endomembrane system** that includes the endoplasmic reticulum (ER), the nuclear membrane, the [Golgi apparatus](https://www.nature.com/scitable/topicpage/how-do-proteins-move-through-the-golgi-14397318), and lysosomes. Membrane components are exchanged throughout the endomembrane system in an organized fashion. For instance, the membranes of the ER and the Golgi apparatus have different compositions, and the proteins that are found in these membranes contain sorting signals, which are like molecular zip codes that specify their final destination. Mitochondria and chloroplasts are also surrounded by membranes, but they have unusual membrane structures --- specifically, each of these organelles has two surrounding membranes instead of just one. The outer membrane of mitochondria and chloroplasts has pores that allow small molecules to pass easily. The inner membrane is loaded with the proteins that make up the electron transport chain and help generate energy for the cell. The double membrane enclosures of mitochondria and chloroplasts are similar to certain modern-day prokaryotes and are thought to reflect these organelles\' evolutionary [origins](https://www.nature.com/scitable/topicpage/the-origin-of-mitochondria-14232356). **Conclusion** -------------- Membranes are made of lipids and proteins, and they serve a variety of barrier functions for cells and intracellular organelles. Membranes keep the outside \"out\" and the inside \"in,\" allowing only certain molecules to cross and relaying messages via a chain of molecular events The Composition of Biological Membranes ======================================= [Guido Guidotti, PhD](https://jamanetwork.com/searchresults?author=Guido+Guidotti&q=Guido+Guidotti) Author Affiliations *Arch Intern Med. *1972;129(2):194-201. doi:10.1001/archinte.1972.00320020038003 FullText Abstract The main components of biological membranes are proteins, lipids, and carbohydrates in variable proportions. Carbohydrates account for less than 10% of the mass of most membranes and are generally bound either to the lipid or protein components. Myelin has few functions and is made up almost entirely of lipids. In plasma membranes, the weight ratio of lipid to protein is close to 1; in several specialized membranes (ie, mitochondrion and bacterial cells) this ratio is near 2 or 3. Thus, there appears to be a correlation between the number of activities performed by and the amount of protein in a membrane. The main membrane lipids are phospholipids, cholesterol, and glycolipids. Glycolipids seem to be cell antigens, and they, together with glycoproteins, may determine surface characteristics of a cell which distinguish it from other cells. Approximately ten polypeptide chains of different molecular weights make up most of the mass of protein in plasma membranes. Plasma membrane --------------- Plasma membrane is also referred to as the cell membrane. It is the membrane found in all cells, that separate the inner part of the cell from the exterior. A cell wall is found to be attached to the plasma membrane to its exterior in plant and bacterial cells. Plasma membrane is composed of a lipid layer which is semipermeable. It is responsible to regulate the transportation of materials and the movement of substances in and out of the cell. **Download Complete Chapter Notes of Cell: The Unit of Life**\ [Download Now](javascript:void(0)) In addition to containing a lipid layer sitting between the phospholipids maintaining fluidity at a range of temperatures, the plasma membrane also has membrane proteins. This also includes integral proteins passing through the membrane which act as membrane transporters and peripheral proteins attaching to the sides of the cell membrane. It loosely serves as enzymes which shape the cell. Plasma membrane is selectively permeable to organic molecules and ions, it regulates the movement of particles in and out of organelles and cells. **Table of Content ** - - [Plasma Membrane Functions](https://byjus.com/#Plasma%20Membrane%20Functions) - [Plasma Membrane Components](https://byjus.com/#Plasma%20Membrane%20Components) - [Structure of Plasma Membrane](https://byjus.com/#Structure%20of%20Plasma%20Membrane) - [Fluid Mosaic Model](https://byjus.com/#Fluid%20Mosaic%20Model) - [Micellar model of Plasma membrane](https://byjus.com/#Micellar%20model%20of%20Plasma%20membrane) Plasma Membrane Image --------------------- ![Plasma Membrane Structure](media/image11.png) Plasma Membrane Functions ------------------------- This membrane is composed of a phospholipid bilayer implanted with proteins. It forms a stable barrier between two aqueous compartments, which are towards the outside and inside of a cell in plasma membrane. The embedded proteins perform specialized functions which include cell-cell recognition and selective transport of molecules. Plasma membrane renders protection to the cell along with providing a fixed environment within the cell. It is responsible for performing different functions. In order for it allow movement of substances such as white and red blood cells, it must be flexible such that they could alter the shape and pass through blood capillaries. In addition, it also anchors the cytoskeleton to render shape to a cell and in associating with extracellular matrix and other cells to assist the cells in forming a tissue. It also maintains the cell potential. Plasma membrane is responsible for interacting with other, adjacent cells which can be glycoprotein or lipid proteins. The membrane also assists the proteins to monitor and maintain the chemical climate of the cell, along with the assistance in the shifting of molecules across the membrane. ### Lipid bilayer Function Lipid bilayer is a fine membrane comprising double layers of lipid molecules, the membranes form a continuous barrier around cells. The lipid bilayer serves as a barrier keeping proteins, ions and various other molecules where it is required and prevent its inaccurate diffusion. These are impermeable to most of the hydrophilic molecules. In particular, bilayers are impermeable to ions that allow cells to regulate pH and salt concentrations by transportation of ions across its membrane with the use of ion pumps. --------------------------------------------------------------------------------------- **Download: [Answer Key of NEET 2022](https://byjus.com/neet/neet-2022-answer-key/)** --------------------------------------------------------------------------------------- Plasma Membrane -- Components ----------------------------- ### Parts of Plasma membrane It is composed of the following constituents: - Phospholipids -- forms the ultimate fabric of the membrane - Peripheral proteins -- present on the outer or inner surface of phospholipid bilayer but are not implanted in the hydrophobic core - Cholesterol -- folded between the hydrophobic tails of phospholipid membrane - Carbohydrates -- found to be attached to the lipids or proteins on the extracellular side of the membrane, leading to the formation of glycolipids and glycoproteins - Integral proteins -- found to be implanted in the phospholipid bilayer Phospholipids spontaneously self-organize into a bilayer. These interactions with water enables formation of plasma membrane. Proteins are packed between the lipids which constitute the membrane. Such transmembrane proteins enables their passing into cells through channels, gates or pores which otherwise could not enter. Hence, cells regulate the molecule flow and also perform other roles such as cell recognition and signaling. Carbohydrates usually seen in the plasma membrane form a part of glycoproteins which take form when carbohydrates associate with proteins. The glycoproteins are significantly involved in the interaction taking place between cells which includes cell adhesion. Structure Of Plasma Membrane -- Bio membrane structure ------------------------------------------------------ Plasma membrane is a fluid mosaic of proteins, lipids and carbohydrates. The plasma membrane picture provided above shows the detailed structure of the plasma membrane. It is impermeable to ions and water-soluble molecules crossing membranes only through carriers, transmembrane channels and pumps. The transmembrane proteins nourish the cell with nutrients, regulate the internal ion concentration and set up a transmembrane electrical potential. Change in a single amino acid in one Cl− channel and plasma membrane pump can lead to human disease cystic fibrosis. On the basis of location of the membrane in the body, lipids can make up anywhere from 20-80% of the membrane, the rest being proteins. It is composed of a phospholipid bilayer, which is two layers of phospholipids back-to-back. Phospholipids are lipids with a phosphate group associated with them. The phospholipids have one head and two tails where the head is polar and water-loving or hydrophilic. Tails on the other hand are nonpolar and water-fearing or hydrophobic. ### Phospholipids of Plasma membrane Phospholipids constitute a main element of biological membranes, they are the most abundant lipids found in the membrane. In addition to membrane changes, these components are also operational in signaling hubs. The assemblage of distinct phospholipids is a defining trait of various compartments of the cell which aim at the phospholipid-binding proteins to those compartments. Phosphatidylethanolamine (PE), Phosphatidylcholine (PC), Sphingomyelin and Phosphatidylserine (PS) usually comprise the framework of biological membranes of animal cells which are stabilized by cholesterol. The phospholipids mentioned are distributed asymmetrically between the two halves of the bilayer membrane. The inner leaflet of the membrane consists of the phosphatidylserine and phosphatidylethanolamine predominantly while the outer leaflet mainly comprises the sphingomyelin and phosphatidylcholine. Fluid Mosaic Model ------------------ The description of the structure of plasma membrane can be carried out through the fluid mosaic model as a mosaic of cholesterol, carbohydrates, proteins and phospholipids. First proposed in 1972 by Garth L. Nicolson and S.J. Singer, the model explained the structure of plasma membranes. The model evolved with time however, it still accounts for the functions and structure of plasma membranes the best way. The model describes plasma membrane structure as a mosaic of components which includes proteins, cholesterol, phospholipids, and carbohydrates; it imparts a fluid character on the membrane. Thickness of the membrane is in the range of 5-10nm. The proportion of constituency of plasma membrane i.e., the carbohydrates, lipids and proteins vary from cell to cell. For instance, the inner membrane of the mitochondria comprises 24% lipid and 76% protein, in myelin, 76% lipid is found and 18% protein. **Phospholipids** The chief fabric of this membrane comprises phospholipid molecules that are amphiphilic. The hydrophilic regions of such molecules are in touch with the aqueous fluid outside and inside the cell. The hydrophobic or the water-hating molecules on the other hand are non-polar in nature. One phospholipid molecule comprises a three-carbon glycerol backbone along with 2 fatty acid molecules associated to carbons 1 and 2, and one phosphate-containing group connected to the third carbon. This organisation provides a region known as head to the molecule on the whole. The head, which is a phosphate-containing group possesses a polar character or a negative charge while the tail, another region containing fatty acids, does not have any charge. They tend to interact with the non-polar molecules in a chemical reaction however, do not typically interact with the polar molecules. The hydrophobic molecules when introduced to water, have the tendency to form a cluster. On the other hand, hydrophilic areas of the phospholipids have the tendency to form hydrogen bonds with water along with other polar molecules within and outside the cell. Therefore, the membrane surface interacting with the exterior and interior of cells are said to be hydrophilic. On the contrary, the middle of the cell membrane is hydrophobic and does not have any interaction with water. Hence, phospholipids go on to form a great lipid bilayer cell membrane separating fluid inside the cell from the fluid to the exterior of the cell. **Proteins** The second major component is formed by the proteins of the plasma membrane. Integrins or integral proteins integrate fully into the structure of the membrane, along with their hydrophobic membrane, ranging from regions interacting with hydrophobic regions of phospholipid bilayer. Typically, single-pass integral membrane proteins possess a hydrophobic transmembrane segment consisting of 20-25 amino acids. Few of these traverses only a portion of the membrane linking with one layer whereas others span from one to another side of the membrane, thereby exposing to the flip side. Few complex proteins consist of 12 segments of one protein, highly convoluted to be implanted in the membrane. Such a type of protein has a hydrophilic region/s along with one or more mildly hydrophobic areas. This organisation of areas of the proteins has the tendency to align the protein along with phospholipids where the hydrophobic area of the protein next to the tails of the phospholipids and hydrophilic areas of protein protrudes through the membrane is in touch with the extracellular fluid or cytosol. **Carbohydrates ** The third most important component of the plasma membrane are carbohydrates. They are generally found on the outside of the cells and linked either to lipids to form glycolipids or proteins to form glycoproteins. The chain of this carbohydrate can comprise two to sixty monosaccharide units which could be branched or straight. Carbohydrates alongside peripheral proteins lead to the formation of concentrated sites on the surface of the cell which identify each other. This identification is crucial to cells as they permit the immune system to distinguish between the cells of the body and the foreign cells/tissues. Such glycoproteins and glycoproteins are also observed on the surface of viruses, which can vary thereby preventing the immune cells to identify them and attract them. On the exterior surface of cells, these carbohydrates, their components of both glycolipids and glycoproteins are together known as glycocalyx, which is extremely hydrophilic in nature attracting huge quantities of water on the cell surface. This helps the cell to interact with its fluid-like environment and also in the ability of the cell to acquire substances dissolved in water. Micellar model of Plasma membrane --------------------------------- In 1963, Hilleir and Hoffman suggested that biological membranes can have a non-lamellar pattern. As per them, the plasma membrane has a mosaic of globular subunits referred to as micelles that are densely packed with a central core of lipid molecules with a hydrophilic polar end. As lipid micelles have a tendancy towards spontaneous linking, they are probable building blocks for membranes. The protein components of the membrane in this model can establish a monolayer on either sides of the plane of lipid micelles. It is suggested that the gaps between the globular micelles form water-filled pores which are partially lined by polar groups of micelles and partially by polar groups of associate protein molecules. You just learnt about the structure and different components of plasma membrane. For Plasma membrane notes PDF and to learn some other interesting concepts important for [NEET](https://byjus.com/neet/), visit NEET BYJU'S. Frequently Asked Questions -------------------------- Q1 ### What is a plasma membrane made up of? The structure of plasma membrane is chiefly composed of phospholipid bilayer and proteins. Also, some amount of carbohydrates are present. The composition of both proteins and lipids varies in different cells. Based on the location, the proteins can be peripheral or integral proteins. Q2 ### What is a cell wall? Besides plasma membrane, the cells of algae, fungi and bacteria have a rigid outer structure called the cell wall. This structural layer is found outside the plasma membrane. The cell wall is not found in animal cells. Q3 ### What is lipid bilayer? Lipid bilayer is seen in all cell membranes and is vital as its structural constituents render a barrier marking boundaries of a cell. The structure is referred to as lipid bilayer as it comprises two layers of fat cells. It is arranged in two sheets. Q4 ### What are the components of plasma membrane? Composition of biological membrane -- The main components of the plasma membrane are proteins, lipids and a carbohydrate group which is associated with some of the proteins and lipids. Q5 ### What are the components that are absorbed through plasma? The nutrients that are absorbed from the gut or other structures of origin are carried in plasma such as fats, cglucose, minerals, amino acids and vitamins. Also, plasma contains dissolved carbon dioxide and oxygen in trace quantities and sufficient amounts of nitrogen. Q6 ### What is a bio membrane? A bio membrane or biological membrane is a selectively permeable barrier that defines a cell. The membrane ensures to keep all the toxic substances out of the cell and allows only selected substances to pass through it. Additionally it mediates different cellular activities. The biological membrane comprises a bilayer of lipid molecules. The structure is called phospholipid bilayer. Q7 ### Describe the role of cholesterol in cell membrane. Generally, plasma membrane have a lot of cholesterol as their lipid constituent; it is interspersed between the phospholipid bilayer. It is involved in modulating the bilayer structure of the bio membrane by changing the thickness, fluidity, water penetration, compressibility and intrinsic curvature of lipid bilayers. Cholesterol is the stabilizing molecule which checks the movement of phospholipids at the time of fluctuations in temperature. Q8 ### Where is the plasma membrane hydrophobic? The heads forming the inner and outer linings are hydrophilic while the tails facing the inner side of the membrane are hydrophobic. Q9 ### What is the function of biological membrane? The main functions of biological membranes are -- - It prevents the entry of toxic substances into the cell - Allows passage of selected molecules between the cell and its exterior since it comprises channels and receptors [**Organization, structure and activity of proteins in monolayers**](https://www.sciencedirect.com/science/article/pii/S0927776507001488) ----------------------------------------------------------------------------------------------------------------------------------------- Julie Boucher, \... Christian Salesse, in [Colloids and Surfaces B: Biointerfaces](https://www.sciencedirect.com/journal/colloids-and-surfaces-b-biointerfaces), 2007 The cell membrane is a barrier that controls the exchange of compounds and information between the outer and inner parts of the cell. In order to achieve this function, cell membranes contain embedded [membrane proteins](https://www.sciencedirect.com/topics/neuroscience/transmembrane-protein) that play different roles. Several of families of membrane proteins have been identified, such as (1) channels and pores which control the exchange of ions and water between the inside and outside of the cell (for a review, see \[1--4\]), (2) G-protein coupled receptors that transmit information by [binding ligands](https://www.sciencedirect.com/topics/neuroscience/ligand-binding) located outside of the cell, such as hormones, [neurotransmitters](https://www.sciencedirect.com/topics/chemistry/neurotransmitter), odorants, etc. and, in turn, activate a [signal transduction](https://www.sciencedirect.com/topics/immunology-and-microbiology/signal-transduction) cascade inside the cell that is initiated by G-proteins (for a review, see \[5,6\]), (3) transport selectively nutrients, substrates, [cofactors](https://www.sciencedirect.com/topics/neuroscience/cofactor), etc. \[7\], (4) modulate the concentration of substances inside the cell \[8\] and (5) are involved in cell--cell interactions \[9--11\]. These membrane embedded proteins therefore play major roles in the normal function of cells and are also responsible for several diseases \[12--14\]. We will review the work we have performed to find out the organization and structure of membrane proteins [gramicidin](https://www.sciencedirect.com/topics/neuroscience/gramicidin), [rhodopsin](https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/proteorhodopsin) and [bacteriorhodopsin](https://www.sciencedirect.com/topics/neuroscience/bacteriorhodopsin) by use of the monolayer [model membrane](https://www.sciencedirect.com/topics/immunology-and-microbiology/artificial-membrane) system. [View article](https://www.sciencedirect.com/science/article/pii/S0927776507001488) [**Recent advances in cell membrane camouflage-based biosensing application**](https://www.sciencedirect.com/science/article/pii/S0956566321006606) --------------------------------------------------------------------------------------------------------------------------------------------------- Xiaomeng Yu, \... Jing Zhao, in [Biosensors and Bioelectronics](https://www.sciencedirect.com/journal/biosensors-and-bioelectronics), 2021 ### 1 Introduction Cell membrane is a bio-complex with a thickness of 5--10 nm, and is composed of various bio-macromolecules (Lamparter and Galic, 2020; Singer and Nicolson, 1972). [Lipids](https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/lipid) and proteins are two main components to constitute the cell membrane. On one hand, the membrane-forming [lipids](https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/lipid), containing a hydrophilic head and two hydrophobic alkyl tails, self-assemble into a [lipid bilayer](https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/lipid-bilayer) by dense packing of the hydrophobic tails. Other lipids, such as cholesterol, phosphor-glycerides and [sphingolipids](https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/sphingolipid), endow the membrane with flexibility and fluidity (Aloia et al., 1993; Reading et al., 2017). On the other hand, proteins anchored on the cell membrane mediate the communication and molecular transportation between the cells to maintain the cell [homeostasis](https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/homeostasis) (Nomura et al., 2019). [Membrane proteins](https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/transmembrane-protein) are mainly classified into two categories according to their locations: the peripheral proteins that are tightly connected to the periphery of the cell membrane through electrostatic interaction or [hydrogen bonds](https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/hydrogen-bond), and the integral proteins that insert into cell membranes through hydrophobic interactions (Almén et al., 2009; Phillips et al., 2009). As a natural barrier, cell membrane prevents the exogenous substances from freely entering into the cell on account of the selective permeability, and ensures the integral cell structure to maintain the stable intracellular environment. The delivery of numerous contents in or out the cells are needed to cross the membrane barrier of the cell or organelle, and can be divided into passive transport and active transport (Brangwynne et al., 2009). In the passive transport, [small molecules](https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/small-molecule) pass through the membrane under the control of pressure and concentration differences between the inner and outer of the membrane; in the active transport, [macromolecules](https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/macromolecule) penetrate the membranes with the requirement of the energy consumption and transport carrier. Membrane fusion-based [vesicle transport](https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/vesicular-transporter) is a typical active transport, which can deliver the cargoes, especially proteins, to different destinations through the reconstitution of cell membrane (Jahn et al., 2003). During [membrane fusion](https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/membrane-fusion), an integral and continuous membrane is produced through the gradual amalgamation of two separated membranes, and the process is typically regulated by [fusion proteins](https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/fusion-protein) and influenced by external stimulus (Chernomordik and Kozlov, 2008; Yu and Mella, 2017; Zhao et al., 2016). Soluble-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) are the core fusion proteins in the eukaryotic cells (Bao et al., 2018; D\'Agostino et al., 2017; Xiao et al., 2001); e.g. one vesicle SNARE that resides on transport vesicles and three target SNAREs that locate on the target membrane combine together to form a trans-SNARE complex, forcing two [lipid bilayers](https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/lipid-bilayer) to approach each other and releases the energy to drive the membrane fusion. The lipid components in the membrane, especially cholesterol, are also able to promote the membrane fusion (Barrett et al., 2012; Yang et al., 2017). Cholesterol, accounting for 30--40% of the contents in the membrane of the cell and secretory vesicle, has a direct effect on SNARE-mediated fusion that regulates the formation of fusion pore at the membrane. Moreover, cholesterol changes the fluidity, thickness, compressibility, permeability and inherent curvature of the lipid bilayer. The increase of the cholesterol content in cell membrane even skips the semi-fusion intermediate and accelerates the membrane fusion in a protein-free manner (Yang et al., 2016; Oh et al., 2021). Inspired by the natural composition and transport process of cell membranes, researchers have been trying to extract cell membranes and apply them to biological and biomedical studies. Till now, cell [membrane extraction](https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/membrane-extraction) methods are relatively mature, which mainly include the [polycarbonate](https://www.sciencedirect.com/topics/chemical-engineering/polycarbonate) membrane extrusion method, differential [centrifugation](https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/centrifugation) method, and freeze-thaw centrifugation method. In the extrusion method, the cells cultured into a confluent monolayer are collected and extruded to obtain a homogenous materials through a small extruder containing a polycarbonate film (Fang et al., 2014). In the differential centrifugation method, the cells are separated and collected by using a spatula, and mechanically destroyed by using a homogenizer in a buffer containing [protease inhibitors](https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/protease-inhibitor), which finally obtain cell membranes by using differential centrifugation (Alyami et al., 2020). In the freeze-thaw centrifugation method, the cells are collected by using trypsin digestion or a cell scraper, and are repeatedly frozen and thawed in a hypotonic lysis buffer, which are centrifuged to obtain the cell membranes by using a probe sonicator on ice (Zhu et al., 2020). The maturity of these cell membrane extraction technology has laid a solid foundation for the application of cell membranes. Cell membranes extracted from abundant resources retain the preference to fuse with each other or [biomimetic](https://www.sciencedirect.com/topics/chemical-engineering/biomimetics) membranes as those of [liposomes](https://www.sciencedirect.com/topics/chemical-engineering/liposome) or virus-like vesicles. Moreover, these extracted cell membranes have been found to be endowed with the intrinsic properties of their original cells. For instance, cancer cell membranes carrying the tumor-specific surface antigens have the excellent homologous selectivity to target the tumor with the same source (Wu et al., 2020c); [red blood cell membranes](https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/erythrocyte-membrane) show low [immunogenicity](https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/immunogenicity) and extended drug half-life in the circulation system (Ye et al., 2019); while hybrid membranes combine the properties of both parent membranes, such as prolonged blood circulation of [blood cell](https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/hemocyte) membrane and excellent targeting ability of cancer cell membrane (Jiang et al., 2019). Benefiting from the inherent membrane fusion ability and valuable original cell-derived properties, as well as the mature extraction technology, cell membranes have emerged as a kind of attracting materials for camouflage of various surfaces and materials, and have found successful applications in a range of biological and biomedical researches (Liu et al., 2020b; Yang et al., 2021a). To date, reviews on specific topics of cell membrane camouflage including membrane modification and functionalization, hybrid membranes, and applications in drug delivery and cancer therapy have been available elsewhere (Ai et al., 2021; He et al., 2020; Huang et al., 2020a; Liao et al., 2020; Luo et al., 2021; Roy et al., 2020). However, very few reviews were devoted to the applications in biosensing, an interdisciplinary field dedicated to developing analytical methods for various purposes, such as clinical diagnosis, biological research, and environmental monitoring. In 2017, Osaki and Takeuchi (2017) published a review on a similar topic of membrane-based biosensing applications, but they mainly focused on biosensors that used [artificial cell membranes](https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/artificial-membrane) (especially suspended lipid bilayers) coupled with nanopore technologies. Therefore, there is still a lack of reviews on the applications of cell membrane camouflage in biosensing, which have brought a lot of papers and ground-breaking achievements in the last few years. Table 1 represents some typical examples of such biosensing applications, in which various surfaces (e.g., electrodes and microfluidic chips) and materials (e.g., fluorescent or electrochemical probes and nanomaterials) were camouflaged with cell membranes and realize successful detection or *in situ* imaging of targeted molecules or cells. Herein, we aim to present an up-to-date overview of recent advances in cell membrane camouflage-based biosensing applications with a particular focus on the membranes extracted from natural cells (e.g. [blood cells](https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/hemocyte) and cancer cells) as well as some biomimetic membranes, and share our prospects on the challenges and future research direction of this fast-moving filed. **Source of cell membrane** **Camouflaged surface or material** **Biosensing application** **Target** **Sensing range** **Limit of Detection** **Reference** ----------------------------- ---------------------------------------------------- ------------------------------------------------------ ------------------------------------------- ------------------------------------------------ -------------------------- ----------------------- Red blood cell Gold nanoparticles Colorimetric detection Fibrinogen 0.01--10 mg/mL 0.26 mg/mL Kim et al., (2021a) Gold electrode Electrochemical sensor Glucose 0--10 mM 1.06 mM Kim et al., (2018) Field effect transistor Amperometric detection Melittin, streptolysin O, alpha hemolysin 0.7 fM-70 nM, 0.04 fM-42.8 nM, 0.03 fM-300 nM 0.7 fM, 0.04 fM, 0.03 fM Gong et al., (2019) Leukocyte Carbon fiber electrode *In vivo* electrochemical sensing Dopamine 5--20 μM Not provided Wei et al., (2020) Magnetic γ-Fe~2~O~3~ and florescent quantum dots Isolation and analysis of tumor cells subpopulations BT474, MDA-MB-453, and MDA-MB-231 cells 25-10000 cells/mL 25 cells/mL Li et al., (2020b) Platelet Fluorescent polystyrene nanoparticles Single-particle detection Fibrinogen 30--300 μg/mL 3.9 μg/mL Chen et al., (2021a) Microfluidic chip Optical detection Cancer-derived extracellular vesicles 0.1--1000 ng/μL 0.05 ng/μL Kumar et al., (2019) Cancer cell Gold nanoparticles Cell-type-specific imaging HeLa cell Not provided Not provided Xie et al., (2020) Dendritic mesoporous silica nanoparticles Ratiometric photoacoustic biosensing microRNA-21 10 pM-100 nM 11.69 pM Zhang et al., (2019b) Azidosugar-functionalized metal-organic frameworks Differential diagnosis of cancer cell subtypes HeLa, MCF-7, and MDA-MB-231 cells Not provided Not provided Liu et al., (2021) Kidney cell Screen-printed carbon electrode Electrochemical detection Uric acid 0--1000 μM 8.5 μM Kim et al., (2021b) Embryonic kidney cell Modified glass carbon electrode Electrochemical detection Capsaicin, allicin, sanshool 1-100 fM, 10--1000 fM, 1--1000 fM 1 fM, 10 fM, 1 fM Xiao et al., (2021) Hybrid cell Fe~3~O~4~\@SiO~2~ nanoparticles Isolation and detection of circulating tumor cells MCF-7 cell 1-1000 cells 1 cell Ding et al., (2020a) Magnetic beads Isolation and detection of circulating tumor cells MCF-7 cell 10-200 cells 10 cell Rao et al., (2018) Liposome Molecular beacons Extracellular vesicle liquid biopsy Exosomal proteins and RNA 1-Fold--1000-fold dilution of initial vesicles Single vesicle level Zhou et al., (2020a) Molecular beacons Detection of exosomal RNAs Exosomal microRNA-21 10^6^-10^10^ exosomes/mL 10^6^ exosomes/mL Yang et al., (2018) Virus-mimicking vesicle Molecular beacons Detection of exosomal microRNAs Exosomal microRNA-21 1--100 nM 1.3 nM Gao et al., (2019) Read more [View article](https://www.sciencedirect.com/science/article/pii/S0956566321006606) [**Insights into cellular signaling from membrane dynamics**](https://www.sciencedirect.com/science/article/pii/S0003986121000448) ---------------------------------------------------------------------------------------------------------------------------------- Parijat Sarkar, Amitabha Chattopadhyay, in [Archives of Biochemistry and Biophysics](https://www.sciencedirect.com/journal/archives-of-biochemistry-and-biophysics), 2021 ### 1 Introduction Cell membranes are complex *quasi* two-dimensional, cooperative assemblies of a wide variety of [lipids](https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/lipid), proteins and carbohydrates. Membranes provide an identity to the cell and its organelles, and represent an appropriate environment for proper functioning of [membrane proteins](https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/transmembrane-protein) and receptors \[1\]. In addition, the plasma membrane allows morphological compartmentalization of cells, and acts as the selectively permeable interface through which cells sense the external environment and communicate with each other. Contrary to textbook descriptions of membranes \[2\], cell membranes are often highly crowded with a high protein density \[3,4\]. This implies that various membrane components (such as lipids, proteins and the underlying cytoskeleton) must interact with each other efficiently to carry out their optimal function in the membrane. [Biological membranes](https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/biomembrane) carry out many cellular functions that are predominantly mediated by membrane proteins. Interestingly, \~30% of all [open reading frames](https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/open-reading-frame) (ORFs) are predicted to encode membrane proteins \[5\] and \~50% of all proteins encoded by eukaryotic genomes are membrane proteins \[6\]. It is therefore not surprising that membrane proteins represent prime candidates for drugs in all clinical areas \[7--9\]. Membrane proteins mediate a wide range of essential [cellular processes](https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/cellular-processes) such as signaling across the membrane, cell-cell recognition and [membrane transport](https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/membrane-transport). An important function carried out by membrane proteins is [cellular signaling](https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/signal-transduction) which enables the intracellular machinery to communicate and crosstalk with the cellular exterior. Although signaling by membrane proteins is routinely measured based on specific biochemical readouts, involvement of membrane dynamics in analyzing cellular signaling is relatively rare. In this context, lateral diffusion of membrane components represents a fundamental physical process that governs the dynamics of protein-protein and lipid-protein interactions in the membrane and plays a crucial role in cellular signaling \[10--14\]. Due to this reason, exploring changes in lateral mobility (diffusion) of membrane components upon signaling offers a novel dynamic approach to monitor cellular signaling from a biophysical perspective. [View article](https://www.sciencedirect.com/science/article/pii/S0003986121000448) [**Application of Atomic Force Microscopy in cell biology**](https://www.sciencedirect.com/science/article/pii/S1084952117300150) --------------------------------------------------------------------------------------------------------------------------------- Yan Shi, \... Hongda Wang, in [Seminars in Cell & Developmental Biology](https://www.sciencedirect.com/journal/seminars-in-cell-and-developmental-biology), 2018 ### Abstract The cell membrane, involved in almost all communications of cells and surrounding matrix, is one of the most complicated components of cells. Lack of suitable methods for the detection of cell membranes *in vivo* has sparked debates on the [biochemical composition](https://www.sciencedirect.com/topics/immunology-and-microbiology/biochemical-composition) and structure of cell membranes over half a century. The development of single molecule techniques, such as [AFM](https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/atomic-force-microscopy), SMFS, and TREC, provides a versatile platform for imaging and manipulating cell membranes in biological relevant environments. Here, we discuss the latest developments in AFM and the progress made in cell membrane research. In particular, we highlight novel structure models and dynamic processes, including the mechanical properties of the cell membranes. [View article](https://www.sciencedirect.com/science/article/pii/S1084952117300150) [**Seeing surfaces: The brain\'s vision of the world**](https://www.sciencedirect.com/science/article/pii/S1571064507000231) ---------------------------------------------------------------------------------------------------------------------------- Heiko Neumann, \... Ennio Mingolla, in [Physics of Life Reviews](https://www.sciencedirect.com/journal/physics-of-life-reviews), 2007 The cell membrane is composed of layers of proteins and [lipid](https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/lipid) molecules that separate the internal and external conducting solution. The membrane acts as a capacitance to build a charge at both sides of the membrane. Without any input current the cell membrane is in a state of dynamic equilibrium in which currents are flowing across the membrane that balance each other, resulting in [zero net](https://www.sciencedirect.com/topics/earth-and-planetary-sciences/net-zero) current flow. The membrane acts as a resistor that blocks ions of different type to freely pass across the barrier. Proteins of different type act as gates that have constant or activity dependent conductances allowing different amounts of ions passing the membrane. A simple description of a piece of membrane takes into account the conductance *C*, the resistance *R* and the resting potential *v*, resembling an *RC* circuit, Fig. 25 (left). Applying [Kirchhoff\'s](https://www.sciencedirect.com/topics/engineering/kirchhoff) second law describes the dynamics of the membrane potential (voltage) given an arbitrary input current *i* (that is injected into the soma of the cell) https://ars.els-cdn.com/content/image/1-s2.0-S1571064507000231-gr025.gif [Sign in to download full-size image](https://www.sciencedirect.com/user/login?returnURL=https%3A%2F%2Fwww.sciencedirect.com%2Ftopics%2Fbiochemistry-genetics-and-molecular-biology%2Fcell-membrane) Fig. 25. Passive circuits modeling the dynamics of the membrane potential. Simple single compartment models of neurons describe the membrane as a layered patch of phospholipid molecules that separate the internal and external conducting solution acting as an electrical capacitance. In its simplest description the membrane is a passive electrical device consisting of the capacitance, *C*, a specific membrane resistance (barrier for ions to flow through the membrane, *R*) and a resting potential driven by a battery (vrest,RC circuit; left panel). A more detailed model of single compartment neuron models takes into account different synaptic interactions, namely excitatory and inhibitory input currents (right panel). The membrane resistance is dependent on the excitatory and inhibitory inputs, respectively (indicated by the arrows; conductance *g* is inverse proportional to the resistance, g=R−1). (A.1)τdv(t)dt=−v(t)+vrest+R⋅i(t) with τ=RC and a resting potential vrest that is in [simulations set](https://www.sciencedirect.com/topics/computer-science/simulation-set) to zero for convenience. [View article](https://www.sciencedirect.com/science/article/pii/S1571064507000231) [**An introduction to computational development**](https://www.sciencedirect.com/science/article/pii/B9780124287655500347) -------------------------------------------------------------------------------------------------------------------------- Sanjeev Kumar, Peter J. Bentley, in [On Growth, Form and Computers](https://www.sciencedirect.com/book/9780124287655/on-growth-form-and-computers), 2003 ### Cell membrane The cell takes great pains to separate itself from its immediate environment: that is to say the cell has a very well defined boundary -- the cell membrane. The immediate purpose of the membrane is to prevent proteins from seeping away. At the same time, however, proteins need to be able to enter and leave the cell in order to affect it. This passage of proteins is not random. Cells exercise specificity: they can select which proteins enter and leave them. To this end, the cell membrane is semipermeable (or selectively permeable, as it is also known), allowing only certain [protein molecules](https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/protein) through. [View chapter](https://www.sciencedirect.com/science/article/pii/B9780124287655500347)[Explore book](https://www.sciencedirect.com/book/9780124287655) [**Multiscale lipid membrane dynamics as revealed by neutron spectroscopy**](https://www.sciencedirect.com/science/article/pii/S0163782722000340) ------------------------------------------------------------------------------------------------------------------------------------------------- V.K. Sharma, E. Mamontov, in [Progress in Lipid Research](https://www.sciencedirect.com/journal/progress-in-lipid-research), 2022 ### 1 Introduction The cell is the smallest unit of life that can live up on its own and hence generally described as the building block of life. [Cell membrane](https://www.sciencedirect.com/topics/materials-science/cell-membrane) is the physical boundary between the cell and its surrounding environment and thus acts as the first layer of [cellular defence](https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/cellular-immunity) against invasion by foreign particles, including toxins and viruses. It is only a few nanometers thick, but entertains many essential cell functions, including communication with the surrounding environment, transport of molecules, and certain metabolic functions. A rough estimate indicates that the cell membranes in a human body wrap an area of about a football field (few acres) \[1\]. In 1925, the first bilayer model for cell membrane was suggested by the Gorter and Grendel \[2\]. They had shown that [lipids](https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/lipid) extracted from red [blood cells](https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/hemocyte) occupied approximately twice the cell\'s [surface area](https://www.sciencedirect.com/topics/chemistry/surface-area), suggesting that cell membranes are formed from the two opposite layers of the lipids, in which hydrophobic tails face each other in the core of the structure, whereas the hydrophilic heads interact with the surrounding water. In 1935, Danielli and Davson \[3\] included proteins, too, in this model and proposed that protein layers are associated with the polar head of the lipids. In 1972, Singer and Nicolson \[4\] developed fluid mosaic model, in which each leaflet of the cell membrane is considered as a two-dimensional homogenous mixture of lipids in the fluid state, integrated with globular assembling of proteins and carbohydrates. The "mosaic" term of this model refers to the mixture of lipids and intrinsic proteins in the membrane. Since the membrane components can move laterally, the model allows for both diffusion of components and local specific gatherings, characterized by "fluid" boundaries. They have also hypothesized that the [compositions](https://www.sciencedirect.com/topics/chemistry/phase-composition) of lipids are different between the two leaflets, which is referred to as membrane asymmetry. Subsequently, newly developed elements were incorporated into this model, mainly in terms of the [composition](https://www.sciencedirect.com/topics/chemistry/phase-composition) and molecular organization, to describe the asymmetry between the two leaflets and the lateral microdomains, or [lipid](https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/lipid) rafts. In 1997, Simons & Ikonen \[5\] and Brown & London \[6\] showed that cell membranes are not a homogenous fluid phase of lipids. On the contrary, lipids are organized into phase-separated microdomains, called [lipid rafts](https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/lipid-raft), having their specific composition and [molecular dynamics](https://www.sciencedirect.com/topics/chemistry/molecular-dynamics), which are different from those in the surrounding fluid phase. It is now well established that the cell membrane is a heterogeneous mixture of lipids, proteins, and other [small molecules](https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/small-molecule), such as carbohydrates. It can be visualised as a laterally compartmentalized assembly of lipids and proteins that is constantly undergoing reorganization, which is the central concept of the lipid raft hypothesis \[5,7,8\]. In these models, the dynamics of lipid domains, including their formation, growth, and fluctuations serve as a regulatory mechanism for complex membrane functions \[9,10\]. Cell membranes have exceptional viscoelastic properties; elastic enough to contain the organelles within the cells, while fluid enough to allow the movements of lipids and proteins, which are essential for the functionality of the cell membranes. They are semi-permeable, which allows exchange of materials from and into the cell, thus enabling various processes such as nutrition or breathing. The extent of structural disorder and molecular motion within a [lipid bilayer](https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/lipid-bilayer) is referred to as [fluidity](https://www.sciencedirect.com/topics/chemistry/fluidity) of the membrane \[11\]. Cell membrane is a highly dynamic structure, in which the position, orientation, and conformation of its components are continuously changing with time. Membrane dynamics is known to play a key role in the fluidity and [viscoelastic behavior](https://www.sciencedirect.com/topics/materials-science/viscoelastic-behavior) of the membrane, and is a prime determinant in a number of [physiological processes](https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/physiological-process), such as [cell signalling](https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/signal-transduction), membrane trafficking, permeability, [vesicles fusion](https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/vesicle-fusion), [*endo*](https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/endocytosis)- or exocytosis, etc. \[12\]. For example, the long-range diffusion of lipid would assist in the cell signalling, whereas the fast local dynamics of lipids would allow the cell to alter the lateral [membrane organization](https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/membrane-topology) necessary for protein-protein interactions. The bending motion of membrane, which occurs at a longer length scale, is impactful in the cell growth and division. The thickness fluctuations play an important role associated with insertion of the proteins. The flip flop motion occurs on relatively larger time scales (\~few hours) and is crucial for maintaining the asymmetry of the lipid bilayer. Nevertheless, fundamentally, the matrix of cell membrane is a lipid bilayer. Due to the high complexity of cell membranes, [model membrane](https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/artificial-membrane) systems (such as liposomes, lipid bilayer, etc.) mimicking the [biological membranes](https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/biomembrane) have attracted much attention in a quest to investigate [biological processes](https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/biological-phenomena-and-functions-concerning-the-entire-organism), such as [membrane fusion](https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/membrane-fusion), membrane trafficking, pore formation, etc. Knowledge of the structure and dynamics of these membrane-mimicking systems is a prerequisite for understanding the fundamental mechanism of interaction between the membrane active agents and the membrane. These systems have been investigated widely to decipher interaction mechanism with various membrane active molecules including drugs \[13\] and [antimicrobial peptides](https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/antimicrobial-peptides) \[14\]. These model systems are also used in a number of other scientific and technological applications, such as targeted drug delivery, cosmetic products, synthesis of [nanoparticles](https://www.sciencedirect.com/topics/chemistry/nanoparticle), and so forth \[15,16\]. The broad range of such applications is made possible by the Janus-faced properties of lipid molecules. Lipids are amphiphilic molecules having a hydrophilic head and hydrophobic chain(s) that self-assemble under favourable conditions in aqueous medium to form liposomes, [lipid bilayers](https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/lipid-bilayer), or even more complex structures. In the presence of water, they self-assemble in a large variety of phases with different structures and morphologies. The shape of the aggregates has been quantitatively described in terms of the packing parameter (*p*), which is the ratio of the hydrocarbon chain volume and the product of the effective head group area and chain length. Systems with a low packing parameter (around 1/3) prefer spherical aggregates, whereas a value of the packing parameter close to unity favours [lamellar structures](https://www.sciencedirect.com/topics/materials-science/lamellar-structure). [Lipid membranes](https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/membrane-lipid) are highly dynamic structures, which exhibit a hierarchy of dynamics that range from individual molecular motions (such as vibrations, lateral diffusion, flip flop, rotational) to collective modes involving many lipid molecules moving in unison (such as membrane bending motions and thickness fluctuations of the membrane) \[17--24\]. Together these wide varieties of dynamical motions span time scales over many decades, from [molecular vibrations](https://www.sciencedirect.com/topics/chemistry/molecular-vibration) taking place in femtoseconds to flip flops over a few hours. Furthermore, the characteristic length scales of each of these motions range from Angstroms for local molecular motions to a few micrometers for macroscopic cell deformations. A schematic of the hierarchical dynamics in [lipid membranes](https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/membrane-lipid) is presented in Fig. 1. The fast local dynamics play an important role in the lateral organization of the membrane, which is necessary for cell signalling and protein-protein interactions. At the same time, relatively slow dynamics at much large length scale play a key role in the [endocytosis](https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/endocytosis) or exocytosis, cell division, and cell fusion. To investigate these motions, various [spectroscopic methods](https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/spectroscopy), such as [nuclear magnetic resonance](https://www.sciencedirect.com/topics/chemistry/nmr-spectroscopy) (NMR) \[19,25--27\], [electron paramagnetic resonance](https://www.sciencedirect.com/topics/chemistry/epr-spectroscopy) (EPR) \[28\], [fluorescence correlation spectroscopy](https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/fluorescence-correlation-spectroscopy) (FCS) \[29\], [dynamic light scattering](https://www.sciencedirect.com/topics/chemistry/photon-correlation-spectroscopy) (DLS) \[30,31\], x-ray photo-correlation spectroscopy (XPCS) \[32\], neutron spin echo (NSE) \[33--39\], quasi-elastic [neutron scattering](https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/neutron-scattering) (QENS) 22,40--51\], and [inelastic neutron scattering](https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/inelastic-neutron-scattering) (INS) \[52--54\] have been employed. Despite the broad range of the spectroscopic techniques applied, most of them are only capable of measuring dynamics on a very limited time and length scale. NMR, FCS, and [DLS](https://www.sciencedirect.com/topics/chemistry/photon-correlation-spectroscopy) tend to measure diffusion on the length scale over a micrometer and the time scale longer than nanoseconds. In this article, we will discuss application of various methods of neutron scattering such as time resolved [small angle neutron scattering](https://www.sciencedirect.com/topics/chemistry/small-angle-neutron-scattering) (SANS), NSE, [QENS](https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/neutron-scattering), and INS to study membrane dynamics over a wide range of time and length scales. Time resolved [SANS](https://www.sciencedirect.com/topics/chemistry/small-angle-neutron-scattering) can be used to observe lipid kinetic described by the rates of trans-bilayer and inter-bilayer exchange, which typically occurs in few hours \[55--58\]. [NSE spectroscopy](https://www.sciencedirect.com/topics/chemistry/spin-echo) can investigate motions on up to sub-microseconds time scale and sub micrometer length scales \[40,44\]. QENS has proven to be an important tool for assessing [lipid membrane](https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/membrane-lipid) dynamics on the timescale of sub- picoseconds to nanoseconds and length scale of a few Angstroms to nanometers \[22,40,41,44\]. [Inelastic neutron scattering](https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/inelastic-neutron-scattering) has been used to study phonon-like dynamics in the lipid membranes, on sub-picoseconds time scale \[52,53\]. Hence, by the combination of these neutron scattering techniques, one can investigate membrane dynamics over a wide range of time scale (from few hours to sub picoseconds) and length scale (from Angstroms to sub micrometers). Moreover, neutron scattering is non-destructive and probe-free, in a sense that it does not interfere with or affect the intrinsic dynamics of lipid molecules. In this article, we review studies of the membrane dynamics performed using various neutron scattering techniques. ![Fig. 1](media/image13.jpeg) [Sign in to download hi-res image](https://www.sciencedirect.com/user/login?returnURL=https%3A%2F%2Fwww.sciencedirect.com%2Ftopics%2Fbiochemistry-genetics-and-molecular-biology%2Fcell-membrane) Fig. 1. Schematic of dynamical processes observed in typical lipid membranes and their corresponding temporal and spatial regimes. Length and time scales accessible by various spectroscopic methods are also included. Presented for direct comparison are: neutron scattering techniques as green squares, x-ray scattering techniques as magenta squares, light scattering techniques as blue squares, and imaging methods as yellow squares. Other spectroscopic methods shown on the leftmost side, such as electron paramagnetic resonance, nuclear magnetic resonance, infrared and dielectric spectroscopy, are not associated with any specific spatial regime but can cover a broad temporal regime. Figure is adapted from ref. \[40\]. (For interpretation of the references to colour in this figure legend, the reader i

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