BC368 Biochemistry of the Cell II Biological Membranes Chapter 11: Part 1 February 10, 2015 Plasma Membrane “Possibly the decisive step [in the origin of life] was the formation of the first cell, in which chain molecules were enclosed by a semi-permeable membrane which kept them together but let their food in.” J. B. S. Haldane, 1954 Plasma Membrane Plasma Membrane Membrane is composed of: A. Lipids Phospholipids Sterols B. Proteins Integral Peripheral C. Carbohydrates Glycolipids Glycoproteins Plasma Membrane Variable components in different membrane types Membrane Lipids Amphiphilic lipids Major types: phospholipids, glycolipids, sterols sphingosine Glycolipid glycerophospholipid sphingophospholipid Phospholipids Two classes: glycerophospholipids (aka phosphoglycerides) and sphingophospholipids Fig 10-7 Phospholipids Two classes: glycerophospholipids (aka phosphoglycerides) and sphingophospholipids Membrane Lipids: 1A. Glycerophospholipids fatty acids; phosphate and polar “head group” on glycerol. Two Vary in the FA’s and head group. Membrane Lipids: 1B. Sphingophospholipids Named for the enigmatic Sphinx Common in nerve and brain cell membranes Membrane Lipids: 1B. Sphingophospholipids Named for the enigmatic Sphinx Sphingosine replaces glycerol, so only 1 FA tail note amide linkage Membrane Lipids: 1B. Sphingophospholipids Example: sphingomyelin Head group = phosphocholine or phosphoethanolamine Glycolipids Two classes: glycosphingolipids and galactolipids Fig 10-7 Membrane Lipids: 2A. Glycosphingolipids Sphingolipids with carbohydrate head group; common on cell surfaces Examples: cerebrosides and gangliosides Glucose or galactose Ganglioside Sugar Sugar Membrane Lipids: 2B. Galactolipids Diglycerides with galatose groups Common in plant (thylakoid) membranes Membrane Lipids: 3. Sterols Cholesterol and cholesterol-like compounds Lipid Components of Membranes Lipid composition varies across different membranes. Fig 11-2 Lipid Components of Membranes Lipid composition varies across the two leaflets of the same membrane. Turnover of Membrane Lipids Fig 10-16 Defects in Membrane Turnover Deposits of gangliosides in Tay Sachs brain Lipid Aggregates Lipids spontaneously aggregate in water as a result of the Hydrophobic Effect. Lipid Aggregates Amphiphilic lipids form structures that solvate their head groups and keep their hydrophobic tails away from water. Above the critical micelle concentration, single-tailed lipids form micelles. Fig 11-4 Lipid Aggregates Fig 11-4 Bilayers can form vesicles enclosing an aqueous cavity (liposomes). Double-tailed lipids form bilayers, the basis of cell membranes. Fig 11-4 Membrane Proteins Integral proteins (includes lipid-linked): need detergents to remove Peripheral proteins: removed by salt, pH changes Amphitropic proteins: sometimes attached, sometimes not Single Transmembrane Segment Proteins Usually alpha-helical, ~20-25 residues, mostly nonpolar. Example: glycophorin of the erythrocyte. Fig 11-8 Multiple Transmembrane Segment Proteins 7 alpha-helix motif is very common. Example: bacteriorhodopsin Fig 11-10 Beta Barrel Transmembrane Proteins Multiple transmembrane segments form β sheets that line a cylinder. Example: porins. Lipid-Linked Membrane Proteins Attached lipid provides a hydrophobic anchor. An important lipid anchor is GPI (glycosylated phosphatidylinositol. Fig. 11-14 Membrane Carbohydrates On exoplasmic face only Membrane Carbohydrates On exoplasmic face only An example is the blood group antigens glycosphingolipids Membrane Dynamics At its transition temperature (TM), the bilayer goes from an ordered crystalline state to an a disordered fluid one. Fig 11-16 Membrane Dynamics Phospholipids in a bilayer have free lateral diffusion. Fig 11-17 Membrane Dynamics Phospholipids in a bilayer have restricted movement between the two faces. Fig 11-17 Membrane Dynamics Flippases, floppases, and scramblases catalyze movement between the two faces. Fluid Mosaic Fluorescent Recovery After Photobleaching Fluorescent tag is attached to a membrane component (lipid, protein, or carbohydrate). Fluorescence is bleached with a laser. Recovery is monitored over time. Fluorescent Recovery After Photobleaching FRAP Movie Protein Mobility in the Membrane Some membrane proteins have restricted movement. May be anchored to internal structures (e.g., glycophorin is tethered to spectrin). Fig. 11-20 Protein Mobility in the Membrane Lipid rafts are membrane microdomains enriched in sphingolipids, cholesterol, and certain lipid-linked proteins. Fig. 11-21 Thicker and less fluid than neighboring domains. Protein Mobility in the Membrane Lipid rafts are membrane microdomains enriched in sphingolipids, cholesterol, and certain lipid-linked proteins. Lipid Rafts Thicker and less fluid than neighboring domains. Nature Reviews Molecular Cell Biology 4, 414-418 (May 2003) Domains of gel/fluid lipid segregation in a model membrane vesicle, which is a mixture of fluid dilaurylphosphatidylcholine phospholipids with short, disordered chains and gel dipalmitoylphosphatidylcholine phospholipids with long, ordered chains. A red fluorescent lipid analogue (DiIC18) partitions into the more ordered lipids, whereas a green fluorescent lipid analogue (BODIY PC) partitions into domains of more fluid lipids. These domains in a model membrane are much larger than the domains of cell membranes.