Lecture Notes for Mar 5, 2009

March 5, 2009 Lipid Bilayer ? The lipid bilayers created by cells are generally about 5nm thick ? They provide a relatively impermeable barrier to most water soluble molecules ? Because the molecule are associate through non-covalent interactions the individual molecules are not held in a set position ? The membrane is a very dynamic structure ? Considered "two dimensional fluid" Two Dimensional (2-D) Fluid ? Individual molecules diffuses freely within each layer of the bilayer ? The average phospholipid can travel the entire length of a bacterial cell in one second ? Phospholipids rarely move from one side of the bilayer to the other ? "Flip-Flop" ? Occurs spontaneously about 1 time per month ? Fig 10-11 Phospholipid Mobility ? The "flip-flop" rarely occurs because the hydrophobic region must move through hydrophilic region ? The level of fluidity depends on several factors ? Temperature: look at oils, butters etc and how temperature affects them ? The composition of the lipids that make up the membrane Temperature & How it Affects Fluidity ? Lipids become more fluid at warm temperatures and more viscous at cold temperatures ? Example: butter at different temperatures ? Each type of membrane has a characteristic freezing point at which it changes from a liquid to a crystalline or gel state ? Some membrane proteins stop working if the membrane passes a certain level of viscosity ? The temperature at which this phase transition takes place depends on the type of lipid molecules that are present ? Organisms whose temperatures fluctuate with the environments must adjust the types of lipids they synthesize to maintain a relatively constant level of membrane fluidity Lipid Composition ? Saturated hydrocarbon chains ? Maximum number of Hyrdogen's present ? Have no double bonds so the hydrogen chains are flexible so the molecule is very flexible ? The molecules pack tightly together ? The resulting substance is more solid (more viscous) ? Example: butter, lard ? Unsaturated hydrocarbon chains ? Have double bonds between carbons ? Restricts motion ? Molecules have rigid kinks ? The molecules can't pack tightly together ? The substance stays fluid at lower temperatures ? Example: oil ? Level of unsaturation has an effect on movement To make a membrane more fluid... ? Increase the number of unsaturated fatty acids ? Also change length of fatty acid chains ? Longer has more contact points so quicker to form a gel ? Use molecules with shorter fatty acid chains ? Incorporate other types of lipids into the membrane ? Example: Cholesterol Membrane Lipids ? Cells make 500-1000 different types of membrane lipid molecules ? Three major classes 1. Phospholipids 2. Cholesterol 3. Glycolipids Phospholipid ? Most abundant types of lipid membrane-most common ? Structure: ? Two fatty-acid hydrocarbon tails ? 14-24 carbons long ? Usually one tail is saturated and other is unsaturated ? Polar head group ? Usually a glycerol molecule ? which is bound to a phosphate group ? which is bound to another polar functional group ? Figure 10-2. The parts of a phospholipid molecule. Phosphatidylcholine, represented schematically (A), in formula (B), as a space-filling model (C), and as a symbol (D). The kink due to the cis-double bond is exaggerated in these drawings for emphasis. ? By using different polar functional groups and fatty acid chains of different lengths or levels of unsaturation, the cell can make many different types of phospholipids ? some have a complete charge, but others have charges that cancel out and make them neutral Cholesterol ? A lot of cholesterol is found in the plasma membrane of eukaryotic cells ? The ratio can be as high as 1 molecule of cholesterol per phospholipid ? Structure: ? Rigid ring structure ? 4 interlocked rings - flat ? Hydrocarbon tail ? Hydroxy group = polar head ? Figure 10-4. The structure of cholesterol. ? The hydrophilic head group of cholesterol is smaller than that of a phospholipid ? Cholesterol can flip-flop across the membrane more easily and more often than phospholipids ? Cholesterol helps to regulate the fluidity of the membrane ? Rigid ring structure aligns with the fatty acid tails of phospholipids ? Rigid molecules prevents molecules from packing together enough to crystallize ? stays at optimal temperatures ? at higher temperatures fluidity not as much affected due to rigid rings ? Figure 10-5. Cholesterol in a lipid bilayer Glycolipids ? These are found on the non-cytosolic side of the membrane ? exterior facing outward ? Make up about 5% of the outer portion of the plasma membrane of animal cells ? not whole membrane ? Function not completely understood ? Structure: ? Similar to a phospholipid, but instead of a phosphate group, the glycerol binds to one or more sugar molecules ? Figure 10-12. Glycolipid molecules Membrane Composition ? The types of lipids and ratios of lipid molecules in a membrane reflects its function ? Different types of cells synthesize different types of lipids ? Different types of membranes within the same cell will have different lipids and ratios ? Each side of the bilayer contains different lipid molecules Membrane Proteins ? The lipids determine the basic structure of a membrane, but function is largely controlled by the membrane proteins ? A membrane can be from 25% to 75% protein (by weight) ? A typical membrane is about 50% lipid and 50% protein ? Figure 10-19. Various ways in which membrane proteins associate with the lipid bilayer. Transmembrane proteins ? The most common type of membrane protein ? Extend all the way through the bilayer with a portion of the protein on both sides of the membrane ? 3 types 1. Single pass - pass once through bilayer (Fig 10-19 #1) 2. Multi-pass - pass through bilayer multiple times (Fig 10-19 #2) 3. Beta-Barrel - beta pleated sheet structures that fold in on itself to make a pore (Fig 10-19 #3) ? For a protein to pass through, the membrane must be amphiphilic ? Polar side chains allow interactions with water on either side of the membrane ? Non-polar side chains allow interactions with the lipid molecules of the bilayer ? Even though the side chains are non-polar, the peptide bond is polar ? In the absence of water, the amino acid backbone must hydrogen bond to itself ? An alpha helix is held together by hydrogen bonds between the amino acid making the helix ? Most transmembrane proteins pass through the membrane as a regular alpha helix ? Figure 10-21. A segment of a transmembrane polypeptide chain crossing the lipid bilayer as an alpha helix Proteins associated with one side ? It's also possible that a protein is only associate with one side ? The protein associated directly with the monolayer ? The protein is covalently linked to a lipid molecule (directly or indirectly) ? A protein may interact (non-covalently) with other proteins that span the membrane ? See Fig 10-19 #4-8