Bilayer membranes cholesterol

Recently, due to increased interest in membrane raft domains, extensive attention has been paid to the cholesterol-dependent liquid-ordered phase in the membrane (Subczynski and Kusumi 2003). The pulse EPR spin-labeling DOT method detected two coexisting phases in the DMPC/cholesterol membranes the liquid-ordered and the liquid-disordered domains above the phase-transition temperature (Subczynski et al. 2007b). However, using the same method for DMPC/lutein (zeaxanthin) membranes, only the liquid-ordered-like phase was detected above the phase-transition temperature (Widomska, Wisniewska, and Subczynski, unpublished data). No significant differences were found in the effects of lutein and zeaxanthin on the lateral organization of lipid bilayer membranes. We can conclude that lutein and zeaxanthin—macular xanthophylls that parallel cholesterol in its function as a regulator of both membrane fluidity and hydrophobicity—cannot parallel the ability of cholesterol to induce liquid-ordered-disordered phase separation. 

Subczynski, W. K., A. Wisniewska, J.-J. Yin, J. S. Hyde, and A. Kusumi. 1994. Hydrophobic barriers of lipid bilayer membranes formed by reduction of water penetration by alkyl chain unsaturation and cholesterol. Biochemistry 33 7670-7681. 

Bolard J, Seigneuret M, Boudet G. Interaction between phospholipid bilayer membranes and the polyene antibiotic amphotericin B lipid state and cholesterol content dependence. Biochim Biophys Acta 1980 599 280. 

In contrast to (VIII), biradical (VII) shows a strong concentration, cholesterol- and temperature-dependent spin-spin interaction. Rey and McConnell41 have analyzed these spectra quantitatively when the concentration of (VII) is varied between 0.025 mole % and 2 mole % in bilayer membranes (70 mole % dimyristoylphosphatidylcholine and 30 mole % cholesterol) at 30°C. The surprising result was obtained that all the spectra can be accounted for quantitatively as the superposition of two spectra, a monomer spectrum [one molecule of (VII)] and a hexamer spectrum [a cluster containing six molecules of (VII)]. Representative data are given in Figs. 8 and 9. 

The Singer and Nicholson (13) model for the plasma membrane, which now receives much support, is basically a smectic liquid crystal consisting of one bilayer of phospholipid (Figure 4a). The phospholipid bilayer contains cholesterol at a concentration which depends on cell type. Embedded in the lipid liquid crystal he protein molecules. Some of these protein molecules transverse the entire lipid bilayer and communicate both with the inside and the outside of the cells. Some of these may... 

Another significant component of many liposome preparations is cholesterol. In natural cell membranes, cholesterol makes up about 10—50% of the total lipid on a molar basis. For liposome preparation, it is typical to include a molar ratio of about 50% cholesterol in the total lipid recipe. The addition of cholesterol to phospholipid bilayers alters the properties of the resultant membrane in important ways. As it dissolves in the membrane, cholesterol orients itself with its polar hydroxyl group pointed toward the aqueous outer environment, approximately even, in a three-dimensional sense, with the glyceryl backbone of the bilayer s phosphodiglyceride components (Fig. 337). Structurally, cholesterol is a rigid component in membrane construction, not having the same freedom of movement that the fatty acid tails of... 

The lipid bilayer is such that the polar heads (often phosphatidylcholine or phosphati-dylethanolamine) of the phospholipids are juxtaposed on the external and internal surfaces of the membrane, causing the ends of the hydrophobic (i.e., long-chained alkyl) portions of the phospholipids to extend inside the membrane. Also contained within the lipid bilayer are cholesterol and other sterols. 

The effects of cholesterol and cholesterol-derived oxysterols on adipocyte ghost membrane fluidity has been studied. It has been found that cholesterol and oxysterols interact differently with rat adipocyte membranes. Cholesterol interacts more with phosphatidylcholine located at the outer lipid bilayer whereas, for example, cholestanone seems to interact more with phospholipids located at the inner layer... 

Although it is clear that complex lipids can be synthesized under laboratory simulations using pure reagents, the list of required ingredients does not seem plausible under prebiotic conditions. Therefore, it is unlikely that early membranes were composed of complex lipids such as phospholipids and cholesterol. Instead, there must have been a source of simpler amphiphilic molecules capable of self-assembly into membranes. One possibility is lipidlike fatty acids and fatty alcohols, which are products of FTT simulations of prebiotic geochemistry [12] and are also present in carbonaceous meteorites. Furthermore, as will be discussed later, these compounds form reasonably stable lipid bilayer membranes by self-assembly from mixtures (Fig. 4a). 

Changes in cholesterol content. A third type of intrinsic change involves alteration in the amount of cholesterol in a membrane (Robertson and Hazel, 1997). Cholesterol can be incorporated into a membrane up to an approximately one-to-one ratio with phospholipids. Most membrane-localized cholesterol is found in the plasma membrane. Cholesterol is an amphipathic molecule, that is, different regions of the molecule have affinities for either polar or nonpolar environments (figure 7.19). In a membrane, the flexible alkyl tip of the molecule penetrates into the bilayer the 3-/1-hydroxyl group remains near the surface of the membrane, near the ester linkages between the acyl chains and the glycerol moiety. 

Cholesterol and membrane proteins, including structural ones such as glycophorin and myelin basic protein and functional ones such as -ATPase, bacteriorhodopsin, and cytochrome c, are important components of biological membranes. Cholesterol-lipid and a number of protein-lipid interactions have therefore been extensively investigated by vibrational spectroscopy. Interactions of hormones and toxins with phospholipid bilayers were also investigated. 

Stockton, G. W. and Smith, I. C. P. (1976). A deuterium NMR smdy of the condensing effect of cholesterol on egg phosphatidylcholine bilayer membranes. 1. Per-deuterated fatty acid probes. Chem. Phys. Lipids 77 251. 

The occurrence of cholesterol and related sterols in the membranes of eukaryotic cells has prompted many investigations of the effect of cholesterol on the thermotropic phase behavior of phospholipids (see References 23-25). Studies using calorimetric and other physical techniques have established that cholesterol can have profound effects on the physical properties of phospholipid bilayers and plays an important role in controlling the fluidity of biological membranes. Cholesterol induces an intermediate state in phospholipid molecules with which it interacts and, thus, increases the fluidity of the hydrocarbon chains below and decreases the fluidity above the gel-to-liquid-crystalline phase transition temperature. The reader should consult some recent reviews for a more detailed treatment of cholesterol incorporation on the structure and organization of lipid bilayers (23-25). 

Cholesterol is a major hpid component of mammahan cell plasma membranes, accounting for approximately 35% of the total lipid of the membrane. Cholesterol has a chemical structure that is very different from the major polar hpid constiments, which is a consequence of the fused ring system of cholesterol that gives this hpid less conformational flexibihty than the straight chains of the polar lipids. It is thus not surprising that cholesterol does not mix well in membranes and that cholesterol segregates as crystals at around 50-60 mol% in bilayers of several lipids and at a much lower mol fraction of cholesterol in bilayers comprising hpids with unsaturated acyl chains (5). 

Figure 5 Snapshot of a lipid raft system studied through atomistic molecular dynamics simulations (42). Water is shown at the top and at the bottom in light color, while the membrane is in the middle of the figure. In the bilayer, rigid cholesterol molecules are shown in light grey, POPC in dark grey, and sphingomyelin in intermediate grey.

AndreollTE. On the anatomy of amphotericin B-cholesterol pores in lipid bilayer membranes. Kidney Int 1973 4 337-45. DeKruijiff B, Demel RA. Polyene antibiotic-sterol interactions in membranes of Acholeplesma laidlawii cellsand lecithin liposomes. III. Molecular structure of the polyene antibiotic-cholesterol complexes. Biochem Biophys Acta 1974 339 57-70. HoIzRW.Theeffectsofthe polyene antibiotics nystatin and amphotericin Bon thin lipid membranes. Ann N Y Acad Sell 974 235 469-79. 

Apart of forming the bilayer, membrane lipids exhibit dynamic structures within the lamellas, forming microdomains with specific functionalities. The so called membrane rafts are sphingolipid-cholesterol domains that contribute to signal transduction, as well as to lipid and protein sorting and transport [18]. 

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