Cell membrane, phospholipid bilayers

Feverfew s mechanism of action in the prevention of migraine headaches is not known. It is speculated that feverfew affects platelet activity or inhibits vascular smooth-muscle contraction, perhaps by inhibiting prostaglandin synthesis (4). Results of in vitro studies suggest that rather than acting as a cyclooxygenase inhibitor, feverfew inhibits phospholipase A2, thus inhibiting release of arachidonic acid from the cell membrane phospholipid bilayer (11,12). 

Phospholipids are the most important of these liposomal constituents. Being the major component of cell membranes, phospholipids are composed of a hydrophobic, fatty acid tail, and a hydrophilic head group. The amphipathic nature of these molecules is the primary force that drives the spontaneous formation of bilayers in aqueous solution and holds the vesicles together. 

A very brief description of biological membrane models, and model membranes, is given. Studies of lateral diffusion in model membranes (phospholipid bilayers) and biological membranes are described, emphasizing magnetic resonance methods. The relationship of the rates of lateral diffusion to lipid phase equilibria is discussed. Experiments are reported in which a membrane-dependent immunochemical reaction, complement fixation, is shown to depend on the rates of diffusion of membrane-bound molecules. It is pointed out that the lateral mobilities and distributions of membrane-bound molecules may be important for cell surface recognition. 

Cell membranes are bilayers of amphipathic acids, for example phospholipids and sterols, which contain globular proteins. The structure is governed by the essential requirement for stability in an aqueous environment, that is, the hydrophobic tails of the lipid molecules point towards each other, leaving the outer surfaces composed of polar, hydrophilic groups. 

There has been a surge of research activity in the physical chemistry of membranes, bilayers, and vesicles. In addition to the fundamental interest in cell membranes and phospholipid bilayers, there is tremendous motivation for the design of supported membrane biosensors for medical and pharmaceutical applications (see the recent review by Sackmann [64]). This subject, in particular its biochemical aspects, is too vast for full development here we will only briefly discuss some of the more physical aspects of these systems. The reader is referred to the general references and some additional reviews [65-69]. 

Section 26 4 Phospholipids are intermediates in the biosynthesis of triacylglycerols from fatty acids and are the principal constituents of the lipid bilayer component of cell membranes... 

Lipid bilayer (Section 26 4) Arrangement of two layers of phospholipids that constitutes cell membranes The polar termini are located at the inner and outer membrane-water interfaces and the lipophilic hydrocarbon tails cluster on the inside... 

Phospholipids are found widely in both plant and animal tissues and make up approximately 50% to 60% of cell membranes. Because they are like soaps in having a long, nonpolar hydrocarbon tail bound to a polar ionic head, phospholipids in the cell membrane organize into a lipid bilayer about 5.0 nm (50 A) thick. As shown in Figure 27.2, the nonpolar tails aggregate in the center of the bilayer in much the same way that soap tails aggregate in the center of a micelle. This bilayer serves as an effective barrier to the passage of water, ions, and other components into and out of cells. 

Langmuir films have been generated not only from phospholipids but also from tetraether lipids (Fig. 14b). Tetraether glycerophospho- and glycoUpids are typical for ar-chaea, where they may constitute the only polar lipids of the cell envelope [154,155]. Tetraether lipids are membrane-spanning lipids, a single monolayer has almost the same thickness as a phospholipid bilayer. 

The lipid bilayer of a cell membrane contains two layers of a phospholipid such as lecithin, arranged tail-to-tail. 

For cells to carry out their functions, glucose and other nutrients must be brought in, and urea and other waste products must be expelled. This would be an impossible task if cell membranes were composed only of phospholipids. Farge protein molecules act as molecular gates through the membranes (see Chapter 13 for the structures of proteins). These proteins are embedded in the bilayers but protrude into the surrounding water and/or into the cell interiors, as Figure 12-19 indicates. 

Liposomes — These are synthetic lipid vesicles consisting of one or more phospholipid bilayers they resemble cell membranes and can incorporate various active molecules. Liposomes are spherical, range in size from 0.1 to 500 pm, and are thermodynamically unstable. They are built from hydrated thin lipid films that become fluid and form spontaneously multilameUar vesicles (MLVs). Using soni-cation, freeze-thaw cycles, or mechanical energy (extrusion), MLVs are converted to small unilamellar vesicles (SUVs) with diameters in the range of 15 to 50 nm. ... 

Different tissues have different lipid compositions. The most common lipid components of membranes are PC and PE. Lipid extracts from brain and lung are also rich in PS heart tissue is rich in PG, and liver is rich in PI [567]. Human blood cells, as ghost erythrocytes (with cytoplasm contents removed), are often used as membrane models. These have different compositions between the inner and outer leaflets of the bilayer membrane. Phospholipids account for 46% of the outer leaflet membrane constituents, with PC and Sph about equal in amount. The inner leaflet is richer in phospholipids (55%), with the mix 19% PE, 12% PS, 7% PC and 5% Sph [567],... 

Figure 6 Intestinal cell membrane model with integral membrane proteins embedded in lipid bilayer. The phospholipid bilayer is 30-45 A thick, and membrane proteins can span up to 100 A through the bilayer. The structure of a typical phospholipid membrane constituent, lecithin is illustrated. (From Ref. 76.)...

The cells of all contemporary living organisms are surrounded by cell membranes, which normally consist of a phospholipid bilayer, consisting of two layers of lipid molecules, into which various amounts of proteins are incorporated. The basis for the formation of mono- or bilayers is the physicochemical character of the molecules involved these are amphipathic (bifunctional) molecules, i.e., molecules which have both a polar and also a non-polar group of atoms. Examples are the amino acid phenylalanine (a) or the phospholipid phosphatidylcholine (b), which is important in membrane formation. In each case, the polar group leads to hydrophilic, and the non-polar group to hydrophobic character. 

To reach such a site, a molecule must permeate through many road blocks formed by cell membranes. These are composed of phospholipid bilayers - oily barriers that greatly attenuate the passage of charged or highly polar molecules. Often, cultured cells, such as Caco-2 or Madin-Darby canine kidney (MDCK) cells [1-4], are used for this purpose, but the tests are costly. Other types of permeability measurements based on artificial membranes have been considered, the aim being to improve efficiency and lowering costs. One such approach, PAMPA, has been described by Kansy et al. [5],... 

It has been suggested [6] that these unusual sterols, especially in those cases where these unusual sterols comprise the entire sterol content of the organisms, likely replace conventional sterols as cell-membrane components. Evidence for this comes from subcellular fractionation and subsequent analysis of two marine sponges [10]. The sterol composition of the membrane isolates was found to be identical to that of the intact sponge. Most common variation of the marine sterol is in the side-chain, situated deep in the lipophylic environment of the phospholipid bilayer. This suggests that unusual fatty acids might accompany the sterols, and indeed this is often the case [8]. 

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