BIOC290_2a The Lipid Bilayer UPDATED 2 PDF

Molecular Biology of the Cell Membrane Structure  CHAPTER CONTENTS THE LIPID BILAYER MEMBRANE PROTEINS  Cell Membrane Cell membranes are crucial to the life of the cell ✓ The plasma membrane encloses the cell, ✓ Defines its boundaries, ✓ Maintains the essential d...

Molecular Biology of the Cell Membrane Structure  CHAPTER CONTENTS THE LIPID BILAYER MEMBRANE PROTEINS  Cell Membrane Cell membranes are crucial to the life of the cell ✓ The plasma membrane encloses the cell, ✓ Defines its boundaries, ✓ Maintains the essential differences between the cytosol and the extracellular environment, ✓ Contains proteins that act as sensors of extracellular signals, allowing the cell to change its behavior in response to environmental signals, including signals from other cells. Biological membranes: different functions BUT all have common structure A three dimensional schematic view of a cell membrane and the general deposition of its lipid and protein constituents  THE LIPID BILAYER The lipid bilayer provides the basic structure for all cell membranes Lipid molecules constitute about 50% of the mass of most animal cell membranes, nearly all of the remainder being protein. Introduction It is easily seen by electron microscopy An electron micrograph of a segment of the plasma membrane of a human red blood cell seen in cross section, showing its bilayer structure  THE LIPID BILAYER Membrane bilayer structure is attributable exclusively to the special properties of the lipid molecules, which assemble spontaneously into bilayers even under simple artificial conditions All of the lipid molecules in cell membranes are amphiphilic Amphiphilic, that is, they have a hydrophilic (“water-loving”) or polar end and a hydrophobic (“water-fearing”) or nonpolar end.  THE LIPID BILAYER Phospholipids Spontaneously Form Bilayers The shape and amphiphilic nature of the phospholipid molecules cause them to form bilayers spontaneously in aqueous environment Hydrophilic molecules dissolve readily in water because they contain charged groups or uncharged polar groups that can form either favorable electrostatic interactions or hydrogen bonds with water molecules Hydrophobic molecules are insoluble in water because all, or almost all, of their atoms are uncharged and nonpolar and therefore cannot form energetically favorable interactions with water molecules How hydrophilic and hydrophobic molecules interact differently with water Non polar groups are Non polar groups are shown in shown in grey. grey. 2-methylpropane is Acetone is polar, it forms hydrogen hydrophobic. No bonds in acetone. It forms a favorable interactions. favourable electrostatic interaction Icelike cages are (yellow bond) as water is also polar formed, Packing arrangements of amphiphilic molecules in an aqueous environment A micelle and a bilayer seen in cross section Phospholipids Spontaneously Form Bilayers Cone-shape These molecules spontaneously form micelles or bilayers in water, depending on their shape Cylinder-shape Phospholipids Spontaneously Form Bilayers The spontaneous closure of a phospholipid bilayer to form a sealed compartment The closed structure is more stable because it avoids the exposure of the hydrophobic hydrocarbons tails to water, which would be energetically unfavorable Phosphoglycerides, Sphingolipids, and Sterols Are the Major Lipids in Cell Membranes The parts of a typical phospholipid molecule Phosphoglycerides, Sphingolipids, and Sterols Are the Major Lipids in Cell Membranes A polar head group The most abundant containing membrane lipids are the phosphate group phospholipids Two hydrophobic hydrocarbon tails In animal, plant, and bacterial cells, the tails are usually fatty acids Phosphoglycerides, Sphingolipids, and Sterols Are the Major Lipids in Cell Membranes head group Phosphate group glycerol saturated fatty acid unsaturated fatty acid Hydrocarbon tails Phosphoglycerides, Sphingolipids, and Sterols Are the Major Lipids in Cell Membranes ▪ The main phospholipids in most animal cell membranes are the phosphoglycerides, which have a three- carbon glycerol backbone ▪ Two long-chain fatty acids are linked through ester bonds to adjacent carbon atoms of the glycerol, and the third carbon atom of the glycerol is attached to a phosphate group, which in turn is linked to one of several types of head group ▪ By combining several different fatty acids and head groups, cells make many different phosphoglycerides Phosphoglycerides, Sphingolipids, and Sterols Are the Major Lipids in Cell Membranes cis-double bond creates a kink in the tail See these useful videos: https://app.jove.com/embed/pl ayer?id=13931&t=1&s=1&fpv =1 Differences in the length and saturation of the fatty acid tails influence how phospholipid https://app.jove.com/embed/pl molecules pack against one another, thereby ayer?id=11656&t=1&s=1&fpv affecting the fluidity of the membrane =1 A schematic of an abundant plasma membrane phosphoglyceride A Which of these groups are charged? B C In the drawing, A can be one of many possible choices (including the positively charged choline or ethanolamine), B is the phosphate moiety, D E C is the glycerol, and D and E are fatty acids. Phosphoglycerides, Sphingolipids, and Sterols Are the Major Lipids in Cell Membranes See this video for attachments of different groups https://youtu.be/Xzpd_dyL2U4?feature=shared Phosphoglycerides, Sphingolipids, and Sterols Are the Major Lipids in Cell Membranes Sphingolipids, which are built from sphingosine rather than glycerol Sphingosine is a long acyl chain with an amino group (NH2) and two hydroxyl groups (OH) at one end (arrows in orange) In sphingomyelin, the most common sphingolipid, a fatty acid tail is attached to the amino group, and a phosphocholine group is attached to the terminal hydroxyl group o The phospholipids Phosphatidylethanolamine, phosphatidylserine, phosphatidylcholine, and sphingomyelin are: ✓ the most abundant ones in mammalian cell membranes ✓ constitute more than half the mass of lipid in most mammalian cell membranes Glycolipids and Cholesterol ▪ In addition to phospholipids, the lipid bilayers in many cell membranes contain glycolipids and cholesterol Glycolipids resemble sphingolipids, but instead of a phosphate- linked head group, they have sugars attached The structure of cholesterol Eukaryotic plasma membranes contain especially large amount of cholesterol—up to one molecule for every phospholipid molecule The structure of cholesterol Cholesterol is a sterol It contains a rigid ring structure, to which is attached a single polar hydroxyl group and a short nonpolar hydrocarbon chain The structure shown is that of cholesterol, an amphiphilic sterol that affects the permeability and fluidity of the membranes in eukaryotic cells. Most prokaryotic membranes lack cholesterol. The structure of cholesterol The cholesterol molecules orient themselves in the bilayer with their hydroxyl group (OH) close to the polar head groups of adjacent phospholipid molecules Phospholipids Spontaneously Form Bilayers A lipid bilayer also has other characteristics that make it an ideal structure for cell membranes One of the most important of these is its fluidity, which is crucial to many membrane functions  THE LIPID BILAYER The Lipid Bilayer Is a Two-dimensional Fluid Membrane fluidity refers to the viscosity of the lipid bilayer of a cell membrane Viscosity of the membrane can affect the rotation and diffusion of proteins and other bio-molecules within the membrane, thereby affecting their functions.  THE LIPID BILAYER The Fluidity of a Lipid Bilayer Depends on Its Composition and Its Temperature The fluidity of cell membrane has to be precisely regulated Certain membrane transport processes and enzyme activities, for example, cease when the bilayer viscosity is experimentally increased beyond a threshold level.  THE LIPID BILAYER Cell membrane fluidity can be influenced by: Phospholipid types and contents Hydrocarbon chain lengths Fatty acids/cis-double bonds Cholesterol Temperature The influence of cis-double bonds in hydrocarbon chains The Fluidity of a Lipid Bilayer Depends on Its Composition Bacteria, yeast, and other organisms whose temperature fluctuates with that of their environment adjust the fatty acid composition of their membrane lipids to maintain a relatively constant fluidity The Fluidity of a Lipid Bilayer Depends on Its Composition Cholesterol modulates the properties of lipid bilayer When cholesterol mixed with phospholipids, it enhances the permeability-barrier properties of the lipid bilayer Although cholesterol tightens the packing of the lipids in a bilayer, it does not make membranes any less fluid At the high concentrations found in most eukaryotic plasma membranes, cholesterol also prevents the hydrocarbon chains from coming together and crystallizing. The Fluidity of a Lipid Bilayer Depends on Its Composition From wikipedia  THE LIPID BILAYER The lipid compositions of the two monolayers of the lipid bilayer in many membranes are strikingly different (asymmetrical) Membrane-bound phospholipid translocators generate and maintain lipid asymmetry The Asymmetry of the Lipid Bilayer Is Functionally Important The asymmetrical distribution of phospholipids and glycolipids in the lipid bilayer of human red blood cells The Asymmetry of the Lipid Bilayer Is Functionally Important In human red blood cell (erythrocyte) membrane, almost all of the phospholipid molecules that have choline—(CH3)3N+CH2CH2OH—in their head group (phosphatidylecholine and sphingomyeline) are in the outer monolayer, whereas, almost all that contain a terminal primary amino group (phosphatidylethanolamine and phosphatidylserine) are in the inner monolayer  THE LIPID BILAYER The Asymmetry of the Lipid Bilayer Is Functionally Important Converting extracellular signals into intracellular ones 1. Signal perception 2. Intracellular 3. Signal cellular signal transduction response Extracellular cytosol environment The Asymmetry of the Lipid Bilayer Is Functionally Important PKC Many cytosolic proteins bind to specific lipid head groups found in the cytosolic monolayer of the lipid bilayer PKC Protein kinase C The Asymmetry of the Lipid Bilayer Is Functionally Important PI3K P Specific lipid head groups must first be modified to create protein-binding sites at a particular time and phase Phosphatidylinositol, one of the minor phospholipids that are concentrated in the cytosolic monolayer of cell membrane PI3K Lipid kinases P Phosphate Phosphatidylinositol (PI) The Asymmetry of the Lipid Bilayer Is Functionally Important The plasma membrane contains various phospholipases that are activated by extracellular signals to cleave specific phospholipid molecules, generating fragments of these molecules that can act as short-lived intracellular mediators The Asymmetry of the Lipid Bilayer Is Functionally Important Phospholipase C Phosphatidylinositol (PI) Fragment 1 Fragment 2 in the released in membrane the cytosol activates stimulates Activates protein Release Ca2+ from Kinase C ER The Asymmetry of the Lipid Bilayer Is Functionally Important Animals exploit the phospholipid asymmetry of their plasma membranes to distinguish between live and dead cells When animal cells undergo apoptosis, phosphatidylserine rapidly translocates to the extracellular monolayer. The phosphatidylserine exposed on the cell surface signals neighboring cells, such as macrophages, to phagocytose the dead cell and digest it Please see this video for role of certain proteins (flippase, floppases and scramblase) in membrane asymmetry: https://app.jove.com/embed/player?id=12550&access=d24f39d800&t=1&s=1&fpv=1 The Asymmetry of the Lipid Bilayer Is Functionally Important The translocation of the phosphatidylserine in apoptotic cells is thought to occur by two mechanisms: 1. The phospholipid translocator that normally transports this lipid from outer monolayer to the inner monolayer is inactivated 2. A “scramblase”-which are ATP independent transporters, that transfers phospholipids nonspecifically in both directions between the two monolayers is activated You can watch this video to see how apoptosis can be detected using PI staining and annexin V: https://app.jove.com/embed/player?id=5650&access=f66f06195 c&t=1&s=1&fpv=1  THE LIPID BILAYER-Glycolipids Glycolipids Are Found on the Surface of All Eukaryotic Plasma Membranes Sugar-containing lipid molecules called glycolipid have the most extreme asymmetry in their membrane distribution These molecules, whether in the plasma membrane or in intracellular membranes, are found exclusively in the monolayer facing away from the cytosol In animal cells, they are made from sphingosine, just like sphingomyelin.  THE LIPID BILAYER-Glycolipids and gangliosides Glycolipids occur in all eukaryotic cell plasma membranes, where they generally constitute about 5% of the lipid molecules in the outer monolayer The most complex of the glycolipid, the gangliosides Gangliosides contain oligosaccharides with one or more sialic acid moieties, which give gangliosides a net negative charge The most abundant of the more than 40 different gangliosides that have been identified are in the plasma membrane of nerve cells (5-10% of the lipid mass)  THE LIPID BILAYER-Glycolipids The function of glycolipids come from their localization In the plasma membranes of Epithelial cells, glycolipids may help to protect the plasma membrane against the harsh conditions frequently found there Charged glycolipids may be important because of their electrical effects Glycolipids also function in cell-recognition processes Some glycolipids provide entry points for certain bacterial toxins and viruses (e.g. Vibrio cholerae and polyomaviruses. Polyomaviruses are small, nonenveloped DNA viruses Glycolipids Are Found on the Surface of All Eukaryotic Plasma Membranes Glycolipid molecules. (A) Galactocerebroside is called a neutral glycolipid because the sugar that forms its head group is uncharged. (B) A ganglioside always contains one or more negatively charged sialic acid moieties. There are various types of sialic acid; in human cells, it is mostly N-acetylneuraminic acid, or NANA, whose structure is shown in (C). Whereas in bacteria and plants almost all glycolipids are derived from glycerol, as are most phospholipids, in animal cells almost all glycolipids are based on sphingosine, as is the case for sphingomyelin (Gal = galactose, Glc = glucose, GalNAc = N-acetylgalactosamine; For information: GM1 (monosialotetrahexosylganglioside) the these three sugars are uncharged "prototype" ganglioside, is a member of the ganglio series of gangliosides which contain one sialic acid residue. GM1 gangliosidosis has both central nervous system and systemic findings; while, GM2 gangliosidosis is restricted primarily to the central nervous system.  Some questions… Biological membranes show asymmetry structure. What factors contribute to this feature: 1. uneven distribution of different types of lipids in the inner and outer layers 2. proteins 3. carbohydrates 4. All the above also contribute to membrane asymmetry Scramblases are ATP-independent transporters that allow the random movement of lipids in both layers. True False  Some questions… Biological membranes show asymmetry structure. What factors contribute to this feature: 1. uneven distribution of different types of lipids in the inner and outer layers 2. proteins 3. carbohydrates 4. All the above also contribute to membrane asymmetry Phosphatidylinositol (PI) is present in the inner layer of a membrane; when phosphorylated, it binds and localizes various cytosolic proteins involved in cell signaling. True False