Membranes

The Models of Membrane Structure

1. General Features of the Cell Membrane
   1. The plasma membrane is the boundary that separates the living cell from its nonliving surroundings.
   2. It makes life possible by its ability to discriminate in its chemical exchanges with the environment.
   3. Surrounds the cell and controls chemical traffic into and out of the cell.
   4. Is selectively permeable; it allows some substances to cross more easily than others.
   5. Has a unique structure which determines its function and solubility characteristics.
   6. Intimately involved in cell cell recognition.
2. Early Membrane Model
   1. Lipid and lipid soluble materials enter cells more rapidly than substances that are insoluble in lipids.
      1. Deduction: Membranes are made of lipids.
      2. Deduction: Fat-soluble substance move through the membrane by dissolving in it ("like dissolves like").
   2. Evidence: Amphipathic phospholipids will form an artificial membrane on the surface of water with only the hydrophilic heads immersed in water
      1. Amphipathic = Condition where a molecule has both a hydrophilic region and a hydrophobic region.
         
      2. Deduction: Because of their molecular structure, phospholipids can form membranes. They form either layers or micelles.
   3. Phospholipid content of membranes isolated from red blood cells is just enough to cover the cells with two layers.
      1. Deduction: Cell membranes are actually phospholipid bilayers, two molecules thick.
   4. Membranes isolated from red blood cells contain proteins as well as lipids.
      1. There is protein in biological membranes.
   5. Danielli and Davson (1935) proposed a phospholipid interior with protein coats on both sides.
      The Davson/Danielli Model
      1. Cell membrane is made of a phospholipid bilayer sandwiched between two layers of globular protein.
      2. The polar (hydrophilic) heads of phospholipids are oriented towards the protein layers forming a hydrophilic zone.
      3. The nonpolar (hydrophobic) tails of phospholipids are oriented in between polar heads forming a hydrophobic zone.
      4. Though the phospholipid bilayer is probably accurate, there are problems with the Davson- Danielli model:
         1. Not all membranes are identical or symmetrical.
         2. Membranes with different functions also differ in chemical composition and structure.
         3. Membranes are bifacial with distinct inside and outside faces.
         4. A membrane with an outside layer of proteins would be an unstable structure.
         5. Membrane proteins are not soluble in water, and, like phospholipid, they are amphipathic.
         6. Protein layer not likely because its hydrophobic regions would be in an aqueous environment, and it would also separate the hydrophilic phospholipid heads from water.
3. The Fluid Mosaic Model
   
   1. The Fluid Quality of Membranes
      1. Membranes are held together by hydrophobic interactions.
      2. Most membrane lipids and some proteins can drift laterally within the membrane. (Figure 8.5)
      3. Molecules rarely flip transversely across the membrane, because hydrophilic parts would have to cross the membrane's hydrophobic core.
      4. Phospholipids move quickly along the membrane's plane, averaging 2 um per second.
   2. Membrane proteins drift more slowly than lipids. The fact that proteins drift laterally was established experimentally by fusing a human and mouse cell:
      1. Membrane proteins of a human and mouse cell were labeled with different green and red fluorescent dyes.
      2. Cells were fused to form a hybrid cell with a continuous membrane.
      3. Hybrid cell membrane had initially distinct regions of green and red dye.
      4. In less than an hour, the two colors were intermixed.
   3. Some membrane proteins are tethered to the cytoskeleton and cannot move far.
   4. Membranes solidify if the temperature decreases to a critical point. Critical temperature is lower in membranes with a greater concentration of unsaturated phospholipids.
   5. Because they hinder close packing of phospholipids, the steroid cholesterol and unsaturated hydrocarbon tails (with kinks at the carbon-to-carbon double bonds) enhance membrane fluidity.
   6. Membranes must be fluid to work properly. Solidification may result in permeability changes and enzyme deactivation.
   7. Organisms adapt to cold temperatures by altering membrane lipid composition (e.g. winter wheat increases concentration of membrane unsaturated phospholipids and some hibernating animals enrich membranes with cholesterol).
4. Membranes as Mosaics of Structure and Function
   1. A membrane is a mosaic of different proteins embedded and dispersed in the phospholipid bilayer. These proteins vary in both structure and function, and they occur in two spatial arrangements:
      1. Integral proteins which are inserted into the membrane so their hydrophobic regions are surrounded by hydrocarbon portions of phospholipids. They may be:
         1. unilateral, reaching only part way across the membrane.
         2. transmembrane, with hydrophobic midsections between hydrophilic ends exposed on both sides of the membrane.
   2. Peripheral proteins which are not embedded but attached to the membrane's surface.
      1. May be attached to integral proteins.
      2. On cytoplasmic side, may be held by filaments of cytoskeleton.
5. Membranes are bifacial.
   1. The membrane's synthesis and modification by the ER and Golgi determines this asymmetric distribution of lipids, proteins and carbohydrates:
      1. Two lipid layers may differ in lipid composition.
      2. Membrane proteins have distinct directional orientation.
      3. When present, carbohydrates are restricted to the membrane's orientation.
      4. Side of the membrane facing the lumen of the ER, Golgi and vesicles is topologically the same as the plasma membrane's outside face.
         1. Side of the membrane facing the cytoplasm has always faced the cytoplasm, form the time of its formation by the endomembrane system to its addition to the plasma membrane by the fusion of a vesicle.
6. Membrane Carbohydrates and Cell-Cell Recognition
   1. Cell-cell recognition = The ability of a cell to determine if other cells it encounters are alike or different from itself.
   2. Cell-cell recognition is crucial in the functioning of an organism. It is the basis for:
      1. Sorting of an animal embryo's cells into tissues and organs.
      2. Rejection of foreign cells by the immune system.
   3. The way cells recognize other cells is probably by keying on cell markers found on the external surface of the cell membrane. Because of their diversity and location, likely candidates for such cell markers are membrane carbohydrates:
      1. Usually branched oligosaccharides.
      2. Some covalently bonded to lipids (glycolipids).
      3. Most covalently bonded to proteins (glycoproteins).
      4. Vary from species to species, between individuals of the same species and among cells in the same individual.

---