Membrane lipid bilayers cholesterol interactions

Whereas the main challenge for the first bilayer simulations has been to obtain stable bilayers with properties (e.g., densities) which compare well with experiments, more and more complex problems can be tackled nowadays. For example, lipid bilayers were set up and compared in different phases (the fluid, the gel, the ripple phase) [67,68,76,81]. The formation of large pores and the structure of water in these water channels have been studied [80,81], and the forces acting on lipids which are pulled out of a membrane have been measured [82]. The bilayer systems themselves are also becoming more complex. Bilayers made of complicated amphiphiles such as unsaturated lipids have been considered [83,84]. The effect of adding cholesterol has been investigated [85,86]. An increasing number of studies are concerned with the important complex of hpid/protein interactions [87-89] and, in particular, with the structure of ion channels [90-92]. 

The interactions obviously differed between the lipid bilayers and the natural membranes. Furthermore, cholesterol slightly hinders the drug partitioning into the liquid-crystalline bilayers, in agreement with several previous reports, and the drug molecules interact electrostatically with membrane proteins at the hydrophilic interface adjacent to the polar headgroups of the phospholipid molecules (7). 

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... 

There is a long history of controversy in the literature regarding the mode of action of general anesthetics. Experimental results derived from model systems of lipids alone or lipid-cholesterol are somewhat controversial. To mention just a few, using Raman spectroscopy it was found that, at clinical concentrations, halothane had no influence on the hydrocarbon chain conformations, and it was concluded that the interaction between halothane and the lipid bilayer occurs in the head group region [57]. This idea was also supported by 19F-NMR studies. The chemical shifts of halothane in a lipid suspension were similar to those in water and differed from those in hydrocarbons. In contrast, from 2H-NMR experiments, it was concluded that halothane is situated in the hydrocarbon region of the membrane (see also chapter 3.3). 

The last group of amphiphiles contains sterols that are present in the membranes of cells. The most popular among them is cholesterol (Choi), which can be easily incorporated in lipid bilayers, increasing their rigidity and making them less permeable, due to the interactions taking place with phospholipids in lipid membranes which result in modification of the lipid acyl-chain conformation. 

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). 

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. 

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