Membrane asymmetric distribution

Ion Channels. The excitable cell maintains an asymmetric distribution across both the plasma membrane, defining the extracellular and intracellular environments, as well as the intracellular membranes which define the cellular organelles. This maintained a symmetric distribution of ions serves two principal objectives. It contributes to the generation and maintenance of a potential gradient and the subsequent generation of electrical currents following appropriate stimulation. Moreover, it permits the ions themselves to serve as cellular messengers to link membrane excitation and cellular... 

At a more molecular level, the influences of the composition of the membrane domains, which are characteristic of a polarized cell, on diffusion are not specifically defined. These compositional effects include the differential distribution of molecular charges in the membrane domains and between the leaflets of the membrane lipid bilayer (Fig. 3). The membrane domains often have physical differences in surface area, especially in the surface area that is accessible for participation in transport. For example, the surface area in some cells is increased by the presence of membrane folds such as microvilli (see Figs. 2 and 6). The membrane domains also have differences in metabolic selectivity and capacity as well as in active transport due to the asymmetrical distribution of receptors and transporters. 

Myelin in situ has a water content of about 40%. The dry mass of both CNS and PNS myelin is characterized by a high proportion of lipid (70-85%) and, consequently, a low proportion of protein (15-30%). By comparison, most biological membranes have a higher ratio of proteins to lipids. The currently accepted view of membrane structure is that of a lipid bilayer with integral membrane proteins embedded in the bilayer and other extrinsic proteins attached to one surface or the other by weaker linkages. Proteins and lipids are asymmetrically distributed in this bilayer, with only partial asymmetry of the lipids. The proposed molecular architecture of the layered membranes of compact myelin fits such a concept (Fig. 4-11). Models of compact myelin are based on data from electron microscopy, immunostaining, X-ray diffraction, surface probes studies, structural abnormalities in mutant mice, correlations between structure and composition in various species, and predictions of protein structure from sequencing information [4]. 

While examples such as these provide evidence that strong interactions of negatively-charged membrane lipids with membrane proteins the role in maintaining asymmetric distributions of lipids aaoss biological membranes is unclear. In any event such effects are likely to be of minor importance relative to actively mediated phospholipid translocation processes. 

Asymmetric distribution of phospholipids across the retinal rod outer segment disk membrane has been shown to be associated with light reception by rhodopsin. It is known that the major phospholipids of this membrane, phosphatidylcholine and phosphatidylethanolamine, are symmetrically distributed across the membrane in the dark but not... 

The maintenance of an asymmetric distribution of phospholipids across the plasma membrane with choline phospholipids predominating on the external surface and amino phospholipids confined to the cytoplasmic leaflet of the membrane has now been well estabhshed. The participation of... 

Gascard, P., Tran, P., Sauvage, M., Sulpice, J-C., Fukami, K., Takenawa, T, Qaret, M. and Giraud, F., 1991, Asymmetric distribution ofphosphoinositides and phosphatidic addin the human erythrocyte membrane. Biochim. Biophys. Acta, 1069 27-36. 

Seigneuret, M. and Deveaux, P.F., 1984, ATP-dependent asymmetric distribution ofspin-labeUed phosphohpids in the erythrocyte membrane relation to shape changes. Proc. Natl. Acad. Scl, U.S.A., 81 3751-3755. 

Verkleij, A.J., Zwaal, R.F., Roelofsen, B., Comfurius, P., KasteUjn, D. and van Deenen, L.L.M., 1973, The asymmetric distribution ofphosphoUpids in the human red cell membrane. A combined study using phospholipases and freeze-etch electron microscopy. 

The concept of a specific orientation for integral membrane proteins is quite general. All integral membrane proteins show such an asymmetry. This, coupled with the asymmetric distribution of lipids in the two leaflets, provides the two leaflets with different characteristics. 

The equilibrium (also known as the Donnan effect) established across a semipermeable membrane or the equivalent of such a membrane (such as a solid ion-exchanger) across which one or more charged substances, often a protein, cannot diffuse. Diffusible anions and cations are distributed on the two sides of the membrane, such that the sum of concentrations (in dilute solutions) of diffusible and nondiffusible anions on either side of the membrane equals the sum of concentrations of diffusible and nondiffusible cations. Thus, the diffusible ions will be asymmetrically distributed across the membrane and a Donnan potential develops. 

Plasma membrane lipids are asymmetrically distributed between the two monolayers of the bilayer, although the asymmetry, unlike that of membrane proteins, is not absolute. In the plasma membrane of the erythrocyte, for example, choline-containing lipids (phosphatidylcholine and sphingomyelin) are typically found in the outer (extracellular or exoplasmic) leaflet (Fig. 11-5), whereas phosphatidylserine, phosphatidyl-ethanolamine, and the phosphatidylinositols are much more common in the inner (cytoplasmic) leaflet. Changes in the distribution of lipids between plasma membrane leaflets have biological consequences. For example, only when the phosphatidylserine in the plasma membrane moves into the outer leaflet is a platelet able to play its role in formation of a blood clot. For many other cells types, phosphatidylserine exposure on the outer surface marks a cell for destruction by programmed cell death. 

FIGURE 11-5 Asymmetric distribution of phospholipids between the inner and outer monolayers of the erythrocyte plasma membrane. 

Lipids also show asymmetrical distributions between the inner and outer leaflets of the bilayer. In the erythrocyte plasma membrane, most of the phosphatidylethanolamine and phosphatidylserine are in the inner leaflet, whereas the phosphatidylcholine and sphingomyelin are located mainly in the outer leaflet. A similar asymmetry is seen even in artificial liposomes prepared from mixtures of phospholipids. In liposomes containing a mixture of phosphatidylethanolamine and phosphatidylcholine, phosphatidylethanolamine localizes preferentially in the inner leaflet, and phosphatidylcholine in the outer. For the most part, the asymmetrical distributions of lipids probably reflect packing forces determined by the different curvatures of the inner and outer surfaces of the bilayer. By contrast, the disposition of membrane proteins reflects the mechanism of protein synthesis and insertion into the membrane. We return to this topic in chapter 29. 

The negatively charged phospholipid phosphatidylserine is asymmetrically distributed in mammalian cell membranes, primarily on the inner leaflet. Upon exposure to collagen or thrombin, the distribution of phospholipids changes with increasing phosphatidylserine in the external membrane leaf (I). The increased expression of phosphatidylserine on the outer leaflet of the membrane creates a procoagulant surface on which several steps of the coagulation cascade take place. 

Tab. 1.4 Asymmetrical distribution of phospholipids (mol%) in membranes of influenza viruses [13] and in red blood cells [12]...

Heterogeneity of membrane constituents may also play an important role in the stabilisation of vesicles. Amphiphiles with cationic and anionic head groups can assemble into vesicles that are stable over a year [37]. This effect may be explained by assuming an asymmetric distribution of the two constituents between the two layers. Note that the two layers have curvatures of equal magnitude but opposite sign. How such an asymmetric membrane structure would be maintained through generation of protocells is not obvious, however. 

An electric potential difference is created between the intra- and extracellular layers of the membrane (Fig. 17.1c), called the surface potential, Es. This is due to the ionization of the amine and carboxyl groups, or others such as thio groups of proteins, on the surface of the membrane, which are oriented according to an asymmetric distribution. An electrical double layer is thus formed. 

The ability to measure the distribution of lipids across natural biomembranes is a potentially powerful capability. Natural biomembranes maintain an asymmetric distribution of lipid components across the membrane with the inner leaflet rich in anionic lipids and both leaflets containing proteins and species specific to each... 

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