Lecture 1

• Fluid mosaic model


  Proposed by Singer and Nicholson in 1972 to describe the structure of cell membranes
• Fluid mosaic model


  • Fluid - due to mobility of lipids and some proteins
  • Mosaic - composed of many different lipids and proteins
• Lipid bilayer


  The membrane is composed of two layers or leaflets of lipids
• Phospholipid


  A type of lipid with a hydrophilic head group and two hydrophobic tails, an amphipathic molecule
• Lipid components of membranes

  • Phospholipids
  • Sterols
  • Glycolipids
• Phosphoglycerides


  A type of phospholipid with a glycerol group
• Phosphatidylcholine (lecithin)


  A common phosphoglyceride with a choline head group
• Saturated fatty acid


  Hydrocarbon tails with only single bonds
• Unsaturated fatty acid


  Hydrocarbon tails with one or more cis double bonds, causing kinks
• Spontaneous self-association of phospholipids in aqueous environment

  1. Polar head groups interact with water

  2. Hydrophobic tails interact with each other

  3. Forms a lipid bilayer
• Lipid bilayer curls to form a sphere, creating a liposome
• Fluidity of lipid bilayer

  • Phospholipids can undergo lateral diffusion, rotation, and flexing within the leaflets
  • Rarely flip-flop between leaflets
• Lower temperature


  Increases viscosity of lipid bilayer
• Membrane fluidity regulation


  • Altering phospholipid saturation (more unsaturated fatty acids)
  • Changing phospholipid tail length (shorter tails)
• Cholesterol can stiffen animal cell membranes and reduce permeability
• Hydrophobic interactions


  Packing of molecules closely together without much movement
• If it gets colder

  Cells need to adapt
• Adaptation to cold


  • Adding unsaturated hydrocarbon chains with Cy double bonds to create kinks
  • Shortening phospholipid tail length
• Adding unsaturated hydrocarbon chains with Cy double bonds

  Increases fluidity by creating kinks and reducing hydrophobic interactions
• Shortening phospholipid tail length

  Increases fluidity by reducing hydrophobic interactions and allowing more flexion and rotation
• Fluid mosaic model


  Model of cell membranes that must remain fluid
• Cholesterol


  A key lipid component of animal cell membranes that decreases mobility of phospholipid tails, stiffens the membrane, and decreases permeability to polar molecules
• There can be up to a 1:1 ratio of cholesterol and phospholipids in cell membranes
• Cholesterol is a rigid, planar, hydrophobic molecule that inserts itself between phospholipids, acting as a wedge to stiffen the membrane
• Lipid bilayers form due to the hydrophobic interactions of the fatty acid tails being repelled from water
• Adding cholesterol to a phospholipid membrane


  Reduces thermal movement, increases membrane thickness, and decreases water permeability
• Scramblases/Phospholipid translocators


  Enzymes that catalyze the rapid flip-flop of random phospholipids from one leaflet to the other in the ER membrane
• Phospholipids are synthesized in the cytosolic leaflet of the ER membrane, requiring scramblases to flip them to the other leaflet to maintain an even distribution
• Flip-flop of phospholipids between membrane leaflets rarely happens spontaneously, but is catalyzed by specific enzymes
• Asymmetry of lipid distribution

  The two leaflets of a cell membrane can have different compositions of lipids, maintained by the action of flipases
• As transport vesicles bud off from the ER and fuse with the Golgi apparatus and plasma membrane, the lipid asymmetry is maintained without flip-flop
• Flipases in the Golgi membrane sort and distribute specific phospholipids to the cytosolic and non-cytosolic leaflets of the plasma membrane
• Alpha Helix


  Membrane spanning domain
• Amphipathic Alpha Helices


  • Core part has hydrophilic amino acids (red)
  • Outer part has hydrophobic amino acids (green) facing the lipid bilayer
• Options for membrane spanning domains

  • Single Alpha Helix
  • Multiple Alpha Helices
  • Beta Barrel
• Beta Barrel


  Beta sheets forming a barrel-shaped structure
• Functions of membrane protein structures

  • Beta Barrel - Forms pores for substances to go in and out of the cell
  • Amphipathic Alpha Helices - Form hydrophilic pores for substances to go in and out
• Examples of membrane protein functions

  • Transporters and channels
  • Anchors to anchor the cell
  • Signal transduction
  • Enzymes
• 1. ray crystallography


  Technique to determine 3D structure of proteins
• Hydrophobicity plot


  Identifies segments of 20-30 hydrophobic amino acids that likely span the lipid bilayer as an alpha helix