Inside-outside asymmetry, membrane

This asymmetry can be partially attributed to the irregular distribution of proteins within the membranes. An inside-outside asymmetry is also provided by the external location of the carbohydrates attached to membrane proteins. In addition, specific enzymes are lo-... 

As described earlier, the inside-outside asymmetry of membrane proteins is stable, and mobifity of proteins across (rather than in) the membrane is rare therefore, transverse mobility of specific carrier proteins is not likely to account for facilitated diffusion processes except in a few unusual cases. 

There is also inside-outside (transverse) asymmetry of the phospholipids. The choline-containing phospholipids (phosphatidylcholine and sphingomyelin) are located mainly in the outer molecular layer the aminophospholipids (phosphatidylserine and phos-phatidylethanolamine) are preferentially located in the inner leaflet. Obviously, if this asymmetry is to exist at all, there must be limited transverse mobility (flip-flop) of the membrane phospholipids. In fact, phospholipids in synthetic bilayers exhibit an extraordinarily slow rate of flip-flop the half-life of the asymmetry can be measured in several weeks. However, when certain membrane proteins such as the erythrocyte protein gly-cophorin are inserted artificially into synthetic bilayers, the frequency of phospholipid flip-flop may increase as much as 100-fold. 

Asymmetry in the lipid distribution over the bilayer could also be controlled in a similar way by the lateral packing pressure, which is likely to differ between constituent monolayers, due to the distinct chemical environments inside and outside the membrane. The enzymes involved may also be distributed asymmetrically. A configuration with constant, but nonzero, mean curvature, shown in Fig. 5.7, reflects such a situation. A membrane-spatming protein can then be viewed as a sensor of the lateral packing pressure in both monolayers. This speculation has some experimental justification. In a recent study of chromaffin granules, trans-membrane lipid asymmetry was shown to be induced by an ATP-dependent "flippase" [35]. 

My discussion is concerned mainly with the transverse asymmetry in the distribution of plasma membrane enzymes. The scheme shown below indicates an inside-outside distribution pattern which is based on observations from several different laboratories. 

The basic characteristic of the membrane structure is its asymmetry, reflected not only in variously arranged proteins, but also in the fact that, for example, the outside of cytoplasmatic (cellular) membranes contains uncharged lecithin-type phospholipids, while the polar heads of strongly charged phospholipids are directed into the inside of the cell (into the cytosol). 

Components of a photosystem can be inserted selectively into the lipid wall or the inner cavity of the vesicle. For this purpose the lipid and components insoluble in water are dispersed together in aqueous solution by sonification. This leads to an occlusion of water insoluble components within the lipid bilayer. The vesicle membrane is sufficiently stable and impermeable for a number of ions. This allows one to prepare, by gel-filtering, the media of different ionic composition inside and outside the vesicle as shown in Fig. 2b. Such asymmetry of chemical content can be preserved for a rather long time (from several hours to several days). Recently the surfactant molecules with double bonds, which can be polymerized after vesicle preparation, were used for further enhancement of vesicle stability [37-39]. Such polymerized vesicles are stable for several months. 

An observation of vectorial PET across the membranes of lipid vesicles was first reported in 1976 by Mangel [41]. Since then numerous systems for vectorial PET across the membranes of vesicles have been reported (see Table 1, part 1). In spite of the differences between the systems of Table 1, all of them have one important common feature. This feature is the asymmetry of the content of aqueous phases inside and outside the vesicle which is required to provide vectorial PET across the membrane in any system. Note also that each vesicle system of Table 1, may have an analog with reversed topology (i.e. with the reversed contents of the inner and outer aqueous phases). 

The inner and outer components of the membrane bilayer have been shown to possess differing compositions and this is reflected in the different biological properties of the inside and outside of the cell membranes as reviewed by Bretscher [242]. X-Ray analysis of eukaryotic myelin membranes has demonstrated an asymmetric distribution of sterols, with almost double the sterol content in the outer bilayer leaflet as compared to the inner layer [243], This asymmetry is reflected in Figure 3.4. 

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