Biomembranes Transport of Small Molecules Part 1 Cell Membranes Membrane Functions 1 Selective permeability 2 Compartmentalize 3 Localize biochemical reactions 4 Membrane proteins respond to signals energy transduction ATP synthesis structural anchors Basic Structure of the Membrane 3 6 nm See also Lodish 7e Fig 10 1 Lipids are Amphiphilic 1 Phospholipids 2 Sphingolipids 3 Sterols Polar Hydrophilic Hydrophobic 1 Phospholipids Polar Hydrophilic Head Group Nonpolar Hydrophobic Tail phosphatidylcholine double bond See also Lodish 7e Fig 10 8A Unsaturated fatty acid Saturated fatty acid 1 Phospholipids E P S P C P Phosphatidyl ethanolamine PE Phosphatidyl serine PS Phosphatidyl choline PC 1 Phospholipids Phosphatidylinositol PI PI 4 kinase PIP 5 kinase PIP3 also PI PIP PIP2 From Lodish 7e Fig 15 35 2 Sphingolipids Sphinomyelin Glucosylcerebroside See Lodish 7e Fig 10 8b 3 Sterols Cholesterol Polar Head Group Rigid Planar Steroid Ring Structure Nonpolar Hydrocarbon Tail See Lodish Fig 10 8c Behavior of amphiphilic molecules in aqueous solutions van der Waals envelope Glycerophospholipids Sphingolipids Liposomes are models of biological membranes Several hundred Angstroms Phospholipids Stryer Questions from Class 1 Biological Monolayers Thermophiles Archea LDL Particles Lipids can move in the bilayer sheet Transverse diffusion T1 2 several days NEED A FLIPASE Membranes are fluids The Fluidity of the Lipid Bilayer is Temperature Dependent Below Transition Temp Above Transition Temp Thicker Transition temperature is directly proportional to fatty acid chain length and degree of saturation See Lodish 7e Fig 10 9 Questions from Class 2 Why do long saturated fatty acid chains decrease fluidity increase Tt Harder to melt Tt Less fluid long Easier to melt Tt More fluid short Questions from Class 3 Which property saturation or length contributes more to the fluidity transition temperature of membranes Tail Lengt h Transition Temperature oC Doubl e Bonds 0 0 0 0 0 0 0 1 2 3 12 14 16 18 20 22 24 18 18 18 1 23 41 55 66 75 80 1 53 60 All PC D R Silvius Thermotropic Phase Transitions of Pure Lipids in Model Membranes and Their Modifications by Membrane Proteins John Wiley Sons Inc New York 1982 The Fluidity of the Lipid Bilayer is Influenced by Sterol Content Polar Head Groups Cholesterol Stiffened Region More Fluid Region Questions from Class 4 Does cholesterol make membrane more fluid or less fluid At physiological temperatures cholesterol decreases membrane fluidity but at lower temperatures cholesterol makes the membrane more fluid then the phospholipids Therefore it is temperature dependant Life The Science of Biology WH Freeman CHOLESTEROL DOES BOTH IN A TEMPERATURE DEPENDANT FASHION Biological Membranes are Asymetric C P L G L G L G L G C P P S C P P S C P C P C P P S P S C P P S C P P S P S C P P S C P P S C P E P S P E P S P S P E P P S S P E P S P S P E P E P S P E P S P E P C P E P S P S P E P S P E P PC phosphatidylcholine GL glycolipids PS phosphatidylserine PE phosphatidylethanolamine SP sphingomyelin Biomembranes Transport of Small Molecules End Part 1 Biomembranes Transport of Small Molecules Part 2 Membrane Proteins 1 Integral or Intrinsic tightly associated Transmembrane Lipid Anchored Membrane Protein Membrane Protein 2 Peripheral less tightly associated Integral or Intrinsic Membrane Proteins Transmembrane Proteins hydrophilic hydrophobic hydrophilic CYTOSOL FATTY ACID See also Lodish 7e Fig 10 14 Examples of Transmembrane Proteins Bacteriorhodopsin Halobacterium See also Lodish 7e Fig 10 15 7 pass H pump Drives ATP synthesis Examples of Transmembrane Proteins Photosynthetic Reaction Center Rhodopseudomonas H pump 11 pass Examples of Transmembrane Proteins Porins Rhodobacter barrels Examples of Transmembrane Proteins Porins E coli Lodish 7e Fig 10 18 Integral or Intrinsic Membrane Proteins Lipid Anchored Lodish 7e Fig 10 19 Integral or Intrinsic Membrane Proteins Lipid Anchored Acylation Fatty Acid Anchors Prenyl Anchors amide bond thioether bond Lipid Bilayer Ex Myristyl C14 anchor Ex Farnesyl C15 anchor GPI anchors Phosphoethanolamine O Protein C NH CH2 CH2 O P O O O Core Saccharide MAN MAN MAN GLC NH2 HC O C R1 O O O HO OH OH OH HC O C R2 O P O CH2 Phosphatidyl inositol Membrane Proteins Peripheral Membrane Proteins 1 Protein Protein Interactions Lipid Bilayer Non covalent interactions 2 Lipid Binding CYTOSOL Integral membrane proteins can be solubilized with detergents See also Lodish 7e Fig 10 22 Detergent Micelles SDS ionic Triton X 100 non ionic Integral membrane proteins can be solubilized with detergents Protein in bilayer Detergent micelle Detergent monomers See also Lodish 7e Fig 10 23 H2O soluble protein detergent complex Soluble lipid detergent complex Biomembranes Transport of Small Molecules End Part 2 Biomembranes Transport of Small Molecules Part 3 Basic Structure of the Membrane Fluid Mosaic Model Movement of Proteins in the Membrane Mouse Cell Mb Protein Human Cell Mb Protein Fluorescent Marker to Mouse mb protein Each mb Protein Confined to half of cell Mb proteins mixed Fusion heterokaryon Fluorescent Marker to Human Mb protein 0 minutes 40 minutes Fluorescence Recovery after Photobleaching FRAP Lodish 7e Fig 10 10 a b Cells can confine proteins to specific domains Tight Junctions Polarized epithelial cell Protein A TIGHT JUNCTION Protein B Apical Plasma Membrane Lateral Plasma Membrane Basal Plasma Membrane Basal Lamina Tight Junction Cells can confine proteins to specific domains Lipid Rafts Sphingolipid and cholesterol rich certain proteins have an affinity for rafts Lawrence Livermore National Laboratory Self assembly Into large aggregates Interaction with Extracellular macromolecules Interaction with Intracellular macromolecules Interaction with proteins on neighbor cells Cells can also Completely immobilize Proteins in the membrane Biomembranes Transport of Small Molecules End Part 3 Biomembranes Transport of Small Molecules Part 4 Movement of Substances Across Membranes 1 Passive Diffusion Protein Independent 2 Transport Mediated a facilitated diffusion b active transport c coupled transport Protein Dependent 3 Bulk movement large particles proteins a vesicle budding and fusion 1 Passive Diffusion no energy required High Concentration Low Concentration Lodish 7e Fig 11 1 2a Transport Mediated Facilitated Diffusion no energy required High Concentration Low Concentration Uniporter Amino acids Nucleosides Sugars etc See also Lodish 7e Fig 11 3 3