| Current structural model of the membrane
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| The generally accepted model of biomembrane structure is the fluid mosaic model proposed by Singer & Nicolson in the early 1970s. This model represents the membrane as a fluid-like phospholipid bilayer into which other lipids and proteins are embedded (Fig. 7.2). As in liposomes, the polar head groups of the phospholipids are exposed on the external surface of the membrane, with the fatty acyl chains oriented to the inside of the membrane. Whereas membrane lipids and proteins easily move on the membrane surface (lateral diffusion), 'flip-flop' movement of lipids between the outer and inner bilayer leaflets rarely occurs without the aid of an integral membrane enzyme, flippase. Although this model is basically correct, there is also growing evidence that many membrane proteins have limited mobility and are anchored in place by attachment to cytoskeletal proteins; membrane sub-structures, described as lipid rafts, also demarcate regions of membranes with specialized composition and function.
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| Membrane proteins are classified as integral (intrinsic) membrane proteins and peripheral (extrinsic) membrane proteins. The former are embedded deeply in the lipid bilayer and some of them traverse the membrane several times (transmembrane protein), whereas peripheral membrane proteins are bound to membrane lipids and/or integral membrane proteins by noncovalent interactions (Fig. 7.2). Most of the transmembrane segments of integral membrane proteins form α-helices. They are composed primarily of amino acid residues with nonpolar side chains - about 20 amino acid residues forming six to seven α-helical turns are enough to traverse a membrane of 5 nm (50 Å) thickness. The transmembrane domains interact with one another and with the hydrophobic tails of the lipid molecules, often forming complex structures, such as channels involved in ion transport processes (Fig. 7.2).
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| Membrane perturbation by amphipathic compounds |
| Amphipathic compounds have distinct polar and nonpolar moieties. They include many anesthetics and tranquilizers. The pharmacologic activities of these compounds are dependent on their ability to interact with membranes and perturb membrane structure. A number of antibiotics and natural products, such as bile salts and fatty acids, are also amphipathic. While effective at therapeutic concentrations, some of these drugs exhibit detergent-like action in moderate to high concentrations and disrupt the bilayer structure, resulting in membrane leakage. |
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| Figure 7.2 Fluid mosaic model of biomembranes. In the fluid mosaic model, proteins are embedded in a fluid phospholipid bilayer. Glycolipids and glycoproteins are located mainly in the outer leaflet of the plasma membrane. |
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