L5-Organisation of Cell Membrane and Permeability Specialities.pptx

Organisation of Cell Membrane and Permeability Specialities Dr. Bahar ÖZTÜRK KURT 2023-2024 Cell Membrane • A cell is the smallest unit of an organism that can be considered alive. • The pouch or sack is part of the cell itself and is called the cell membrane which is about 6-8 nm thick. • Membra...

Organisation of Cell Membrane and Permeability Specialities Dr. Bahar ÖZTÜRK KURT 2023-2024 Cell Membrane • A cell is the smallest unit of an organism that can be considered alive. • The pouch or sack is part of the cell itself and is called the cell membrane which is about 6-8 nm thick. • Membranes also provide anchorage points for the cytoskeleton which gives shape and rigidity to cells and plays a role in intracellular transport of biomolecules. • Many organelles within the cell also have membrane bound, providing an isolated biophysical environment even within the cell. MEMBRANE STRUCTURE Although biological membranes contain carbohydrates (1-10%) and proteins (~60%), the main structural components of biological membranes are amphipathic lipids (~40%). Amounts of Protein, Lipid and Carbohydrate in Different Biological Membranes (Approximate Percentage of Dry Weight) Membranes Protein Lipid Carbohydrate Plasma membranes: Red blood cells Liver cells Amoeba Myelin 49 54 54 18 43 36 42 79 8 10 4 3 Endoplasmic reticulum 62 27 10 Golgi complex 64 26 10 Mitochondrion; outer membrane inner membrane 55 78 45 22 trace --- Composition of Cell Membrane Membrane Lipids Polar Lipids Non-polar Lipids Membrane Proteins Peripheral Proteins Integral Protein s Carbonhydrates MEMBRANE LIPIDS • The most common lipids found in biological membranes are two-chain phospholipids. • These are molecules with a phosphate head group, attached to a two-chain fatty acid.  The fatty acids are nonpolar chains of carbon and hydrogen. Their nonpolar nature makes them hydrophobic (“water-fearing”).  The phosphate group is polar and hydrophilic (“water-loving”). The amphipathic character comes from the combination of the hydrophilic phosphate head group, along with the hydrophobic, hydrocarbon tails. 1. 2. 3. 4. Nitrogenous chemical group Phosphate group Glycerol Fatty acids In biological membranes, the phospholipids arrange themselves into a bilayer, in which the hydrocarbon tails face each other and are isolated from the surrounding environment by the phosphate head groups. Phospholipid bilayers are fluid: - Hydrogen bonding of water holds the 2 layers together - Individual phospholipids and unanchored proteins can move laterally through the membrane Phospholipid Behavior and Self-Assembly • Phospholipids exhibit a physical behavior that makes them ideal for the formation of membranes. This behavior is call self-assembly. • Self-assembly means that the molecules will aggregate together to form various structures without need for energy input, catalysts, or other helper molecules. Single-chain Phospholipids and Micelle Formation If we slowly add a single-chain phospholipid to an aqueous solution, at first the lipid molecules are dispersed among the water molecules. Later, as the concentration of lipids is increased, a point is reached where the lipid molecules merge together forming aggregates called micelles. A micelle is simply a lipid ball with the hydrocarbon chains pointed in toward the center. The concentration, at which the lipids self-assemble into micelles, is called the critical micelle concentration (CMC). The aggregation process is highly cooperative. Once the critical micelle concentration is reached, any further lipid added to the solution either associates with existing micelles or forms new micelles. There are a number of forces that contribute to self-assembly in micelle formation: • Dispersion forces • Hydrophobic effect • Hydrogen-bond As the hydrocarbon tails approach one another, dispersion forces provide a strong attractive force pulling them together. Close association of the tails is also favored by the hydrophobic effect. As the tails are drawn together, water molecules along the length of the hydrophobic tails are disrupted (disorganized) and excluded (pushed away). Water along the edge of a hydrophobic molecule has its motion restricted; this in turn limits its ability to hydrogen-bond with other water molecules. As the hydrocarbon tails come together, the water along their surface is pushed aside. This increases the entropy of the water by allowing it to rotate freely. The free rotation of the water molecules also increases the possibilities for hydrogen bond formation with other water molecules in solution. The increased entropy and the formation of water-water hydrogen bonds both contribute favorably to the Gibbs energy of micelle formation. Two-chain Phospholipids and Liposome Formation • Micelles can be formed from also two-chain phospholipids, but this is usually not the preferred configuration. • The extra width of the two-chain phospholipids increase the distance between hydrocarbon chains. This reduces the strength of dispersion forces. • The extra width also creates a void in the center of the micelle and increases the size of micelle. • Both the void and the increased size increase the energy cost of micelle formation. • Nature solves this problem by bringing a second layer of lipids opposite the ends of the hydrocarbon chains. • This process is highly cooperative, and it continues aggregating phospholipids until a liposome has formed. • A liposome is a lipid bilayer sphere with a void in the middle. Lipid bilayer Liposome What are the Similarities Between Liposome and Micelle? Both Liposome and micelles are composed of amphipathic molecules. Both Liposome structures. and micelle are vesicular Both Liposome and micelle have significant pharmaceutical applications. Both liposome and micelle play an important role in targeted drug delivery. Formation of both Liposome and micelles increases considerably beyond a particular temperature. What is The Difference Between Liposome and Micelle? In the human body, Micelles help in absorption of lipid and fat-soluble vitamins such as vitamin A, D, E and K. They also help the small intestine in the absorption of essential lipids and vitamins derived from the liver and gallbladder. Liposomes are taken up by organs that are rich in the reticuloendothelial system. Therefore the main objective of liposomes is drug delivery, which is targeted to these organs. In order to target specific tumor cells, the liposomes are coated with special polymers. The relative liposomes production process is costly. Therefore, these liposomes are used only during viral infection treatment and tumor cell killing. Drug administration is achieved via the parenteral route. Artificial lipid vesicles: liposomes (application in medicine. Import of drugs into cells). Liposomes visualized in a freezefracture sample. Electron micrograph Dynamic structure • The bilayer behaves as a two-dimensional fluid, lipid molecules are in continuous motion in the bilayer. • Their fatty acid chains are mobile, and they diffuse in the plane of the bilayer with high velocity (Lateral diffusion) . • They rotate around their long axis. Dynamic structure • A flip-flop translocation of lipids from one lipid layer into the other one is very rare and is only possible with the aid of special enzymes in the living cell. • Plasticity: Due to its dynamic structure, the lipid is able to follow form and volume changes of the cell. Various types of phospholipids are asymmetrically distributed in the two layers of the membrane LIPID BILAYER PERMEABILITY The lipid bilayer is semipermeable meaning that some molecules can pass through the bilayer while others can’t. The ease with which any molecule can pass through the lipid bilayer depends on the energy. LIPID BILAYER PERMEABILITY • The presence of cations has a strengthening effect on the bilayer. • At lower concentrations of cations, the repulsive force of the head groups may assist the large molecules getting through, by making it easier to push the lipids aside. • The strength of the dispersion forces depends largely on the amount of close contact between the hydrocarbon chains. • This in turn depends on how close together the chains can pack and how long the chains are. • Longer chains make stronger dispersion forces and more stable bilayers. Another significant factor is whether the hydrocarbon chains are saturated, unsaturated, or polyunsaturated. FLUID MOSAIC MODEL The current working model of biological membranes is the fluid mosaic model, which was first proposed by Singer and Nicolson in 1972. The model states that biological membranes are composed primarily of a phospholipid bilayer. Other molecules that are part of the membrane structure form a mosaic with the lipid molecules. In the fluid mosaic model, the lipids and other molecules are free to move about within the two-dimensional mosaic. • Biological membranes are most commonly found to be in the fluid state. • In the fluid state, the mobility of molecules within the mosaic plane enhances a cell’s ability to move membrane proteins and receptors around to where they are needed. FACTORS AFFECTING MEMBRANE FLUIDITY • Fluidity of the bilayer structure depends on various factors, like relative amount of cholesterol (rigid molecule), unsaturated fatty acids in the phospholipid molecules and temperature. • The same factors that affect membrane permeability also affect membrane fluidity. • Longer hydrocarbon tails increase dispersion forces. • Conversely, unsaturated lipids and lipids with shorter tails have weaker dispersion forces. • In general, anything that weakens dispersion forces will increase fluidity and permeability. • Anything that strengthens dispersion forces will decrease fluidity and permeability. CHOLESTEROL • Cholesterol is a significant component of many biological membranes, and it has a mixed effect on membrane fluidity. • Cholesterol tends to weaken dispersion forces by positioning itself between the phospholipid molecules. Each cholesterol molecule acts as an unbending barrier that limits some of the motion of the phospholipids. So, while the cholesterol prevents the formation attractive dispersion forces, the steric restriction of phospholipid movement decreases membrane fluidity and increases membrane rigidity. Cholesterol acts as a bi-directional regulator of membrane fluidity; • At high temperatures it stabilizes the membrane • At low temperatures it intercalates between the phospholipids and prevents clustering Proteins • Proteins are the most important molecules of life. • 25-75% of the membrane mass consists of proteins. About 50 lipid molecules per one protein. • These complex macromolecules are made up of long chains of smaller subunits known as amino acids. „Intelligent” properties of the membrane depend on membrane proteins FUNCTIONS OF MEMBRANE PROTEINS Membrane proteins can serve a variety of key functions: •Junctions – Serve to connect and join two cells together •Enzymes – Fixing to membranes localizes metabolic pathways •Transport – Responsible for facilitated diffusion and active transport •Recognition – May function as markers for cellular identification •Anchorage – Attachment points for cytoskeleton and extracellular matrix •Transduction – Function as receptors for peptide hormones ASSOCIATION OF PROTEINS WITH THE LIPID BILAYER • The amino acids of a membrane protein are localised to the membrane according to polarity: • Non-polar (hydrophobic) amino acids associate directly with the lipid bilayer • Polar (hydrophilic) amino acids are located internally and face aqueous solutions Association of proteins with the lipid bilayer Classified by how they are associated with the membrane Two types of membrane proteins 1. Integral membrane proteins 2. Peripheral membrane proteins 1-6 integral membrane proteins 7-8 peripheral membrane proteins 1. Integral membrane proteins • Most integral proteins span the entire phospholipid bilayer. These transmembrane proteins contain one or more membrane-spanning domains. • A transmembrane domain is a membrane-spanning protein domain • Nonpolar regions of the protein are embedded in the interior of the bilayer • Polar regions of the protein protrude from both sides of the bilayer Extensive nonpolar regions within a transmembrane protein can create a pore through the membrane. • • β sheets in the protein secondary structure form a cylinder called a β-barrel β-barrel interior is polar and allows water and small polar molecules to pass through the membrane • Most integral proteins contain residues with hydrophobic side chains that interact with fatty acyl groups of the membrane phospholipids, thus anchoring the protein to the membrane. • These are similar to transmembrane proteins but do not span the bilayer. Their hydrophobic region is embedded into the cytosolic lipid monolayer. • Anchored membrane proteins are located on one side of the bilayer and are attached to it by a covalently bound lipid chain on the cytosolic side or by an oligosaccharide chain covalently bound to phosphatidyl inositol on the extracellular side (glucose phosphate isomerase anchor). • The protein can deport from membrane by detaching from anchor, or can reattached to the membrane by binding back again to the anchor. GPI:glucose phosphate isomerase 2. Peripheral membrane proteins • These are hydrophilic proteins on either the extracellular or cytosolic surface of the membrane and are attached by weak bonds to an integral membrane protein. • They can be removed from the membrane without destruction of the lipid bilayer. peripheral membrane protein integral membrane protein peripheral glycoprotein Peripheral membrane proteins SUGAR CONSTITUENTS : GLYCOCALYX At the extracellular surface of the cell membrane there are short sugar chains (oligosaccharide chains), covalently bound to peripheral proteins or lipids: membrane protein • glycoproteins • glycolipids oligosaccharide chains Some proteins carry long chains consisting of specific sugar molecules (glycosaminoglycan chains, GAGs), they are called proteoglycans. This carbohydrate-rich layer on the extracellular side of the membrane is the glycocalyx. The glycocalyx is a glycoprotein and glycolipid covering that surrounds the cell membranes of bacteria, epithelial cells, and other cells. Functions of Glycocalyx a) The glycocalyx aids in attachment of some cells to extracellular matrix components. b) It binds antigens and enzymes to the cell surface. c) It facilitates cell-cell recognition and interaction. d) It protects cells from injury by preventing contact with inappropriate substances. e) It assists T cells and antigen-presenting cells in aligning with each other. Blood vessel