01. Module 1.pdf

MODULE 1 Slide 1: Learning Objectives Explain the functions of the plasma membrane. Describe how phospholipids, sphingolipids, glycolipids, and cholesterol are arranged in a bilayer and affect the membrane fluidity. Summarize the fluidity factors of the cell membranes. Describe the membr...

MODULE 1 Slide 1: Learning Objectives Explain the functions of the plasma membrane. Describe how phospholipids, sphingolipids, glycolipids, and cholesterol are arranged in a bilayer and affect the membrane fluidity. Summarize the fluidity factors of the cell membranes. Describe the membrane asymmetry and outline its importance. Explain the organization and function of lipid rafts. Slide 2: Plasma Membrane Functions Barrier that protects. Selectively permeable “filter”: transports various molecules. Responds to the environment (via receptors and channels). Secures the attachment to the cytoskeleton. Facilitates cell-cell and cell-ECM interactions. Slide 3: Fluid Mosaic Model The plasma membrane is a fluid combination of lipids, proteins, and carbohydrates attached to lipids/proteins. Outer leaflet. Inner (cytosolic) leaflet. Slide 4: Hydrophobic vs Hydrophilic Hydrophobic molecules are water-insoluble; water molecules form “cages” around them. The free energy is decreased if hydrophobic molecules cluster; this is why lipids aggregate spontaneously in water (i.e., micelles, bilayers). Hydrophilic molecules: water-soluble with polar groups forming electrostatic and hydrogen bonds with water. MODULE 1 Membrane Lipids Phospholipids: - Glycerophospholipids: - Backbone: Glycerol. - Components: - 2 Fatty acids. - PO₄ (Phosphate group). - Alcohol (headgroup). - Sphingolipids: - Backbone: Sphingosine. - Components: - 1 Fatty acid. - PO₄ (Phosphate group). - Choline (headgroup). Glycolipids: - Sphingolipids: - Backbone: Sphingosine. - Components: - 1 Fatty acid. - Mono- or oligosaccharide (sugar headgroup). Sterols: - This category includes cholesterol and other sterol-based lipids, important for membrane structure and fluidity. MODULE 1 Slide 5: Membrane Lipids: Phospholipids Amphipathic: hydrophilic heads, hydrophobic tails. Most abundant membrane lipids: phospholipids (one head, two tails). Tails are fatty acids (~14-24 carbon atoms), with one tail typically having one or more cis-double bonds (i.e., it is unsaturated). Double bonds create a kink in the tail, which increases fluidity; longer tails decrease fluidity. Slide 6: The Four Major Phospholipids Only phosphatidylserine has a net negative charge; the other three lipids are electrically neutral at physiological pH. Slide 7: Glycerol-Based Phospholipids: Phosphoglycerides Glycerophospholipids, also known as phosphoglycerides, are glycerol-based phospholipids. Slide 8: The Lipid Bilayer Is a Two-Dimensional Fluid Lipid molecules move laterally within a monolayer. Lipids rotate about their long axis. Tails swing from side to side and contract. Phospholipids rarely migrate across the bilayer, but this is facilitated by flippases or phospholipid translocators. Phosphatidylserine is usually in the inner leaflet but is redistributed to the outer leaflet during apoptosis. MODULE 1 Slide 9: Cell Membrane Fluidity and Its Factors Lipid bilayers change from a liquid state to a gel state at a freezing point (phase transition). More fluidity if the hydrocarbon chains are short or have double bonds. The hydroxyl groups of cholesterol are positioned close to the head groups of the phospholipids; the steroid rings are close to the hydrocarbon chains (tails). Cholesterol makes the lipid bilayer less fluid at higher temperatures and less rigid at lower temperatures. Slide 10: Glycolipids Sugar-containing lipids on the outer monolayer (leaflet). Self-associate by hydrogen bonds between the sugars and by van der Waals forces between hydrocarbon chains. Protective role: In epithelial cells, glycolipids are on the apical surface, protecting against low pH and enzymes. Cell recognition role: Ganglioside GM1 is a receptor for the bacterial toxin causing the diarrhea of cholera. Slide 11: Gangliosides Are Glycolipids Glycolipids are made of the sphingolipid ceramide and an oligosaccharide with one or more sialic acid residues. Abundant in neurons, primarily in the outer leaflet of the plasma membrane. Involved in cell-cell recognition, adhesion, and signaling. Guillain-Barré syndrome, leading to acute quadriplegia, is caused by an autoimmune response to cell surface gangliosides. Influenza A viruses recognize sialic acid residues on cell surfaces as receptors. Slide 12: Asymmetry of the Lipid Bilayer Typically, phosphatidylcholine and sphingomyelin are in the outer leaflet; phosphatidylserine, phosphatidylethanolamine, and phosphatidylinositol are in the inner leaflet. Glycoproteins are in the outer leaflet with carbohydrates facing the extracellular space. Peripheral membrane proteins are on the inner leaflet, facing the cytoplasm. Cytosolic proteins may bind specific lipid heads. MODULE 1 During apoptosis, phosphatidylserine moves to the extracellular leaflet and signals to the macrophages to phagocytose the dead cell. Asymmetry is created through transporters and spontaneous flip-flop movements. Slide 13: Lipid Rafts Composed of sphingolipids and cholesterol in the outer leaflet. The long, saturated hydrocarbon chains of sphingolipids hold other molecules together. Rafts are thick and concentrate proteins. Slide 14: Putting It Together Biological membranes are a continuous double layer of lipids with embedded proteins. The lipid bilayer is a two-dimensional fluid: Lipid molecules diffuse within the plane. Membrane lipid molecules are amphipathic. Based on the molecular backbone of the lipid, there are three classes of membrane lipids: phospholipids, cholesterol (sterols), and glycolipids. In water, phospholipids assemble into bilayers, which form sealed compartments that reseal if torn. The lipid compositions of the inner and outer monolayers differ, reflecting their different functions. The head groups of some lipids form docking sites for cytosolic proteins. The fluidity of the membrane is affected by factors such as cholesterol content, the length of the fatty acid tails, the number of double bonds in them, headgroup charge, and structure.