Cholesterol in lipid bilayer

The rote of cholesterol in the fluidity of biological membranes is characterized as essential. Cholesterol is a silent molecule and in the case of lipid bilayers and liposomes it is included into bilayers to control the rate of the release of encapsulated molecules or to influence the stability of liposomes. The addition of cholesterol in lipid bilayers composed of DPPC, at concentrations more than 20%, results in the decrease of the Tin and elimination of the pretransition temperature. 

P. Tauc, C.R. Mateo, J-C. Brochon, Pressure effects on the lateral distribution of cholesterol in lipid bilayers A time-resolved spectroscopy study, Biophys. J. 74, 1864-1870 (1998)... 

It is a well-known experimental fact that incorporation of cholesterol in lipid bilayers affects the mechanical and transport properties of membranes. This includes their increased bending elasticity (22) and reduced passive permeability to small molecules (23, 24). Despite a great deal of theoretical and experimental research, no definitive microscopic understanding of phospholipid-cholesterol interactions has been proposed yet. 

Yin, J.-J. and W. K. Subczynski. 1996. Effect of lutein and cholesterol on alkyl chain bending in lipid bilayers A pulse electron paramagnetic resonance spin labeling study. Biophys. J. 71 832-839. 

Another example comes from the work of Johnson, et a/.18 These workers studied spin labels dissolved in lipid bilayer dispersions of dipalmitoylphos-phatidylcholine and cholesterol (9 1 by weight) in the hope that anisotropic rotational diffusion of the spin label would mimic the motion of the bilayer components. In addition to 5-DS, which is sensitive to rotational motion about the NO bond, they used the steroidal nitroxide 8, which tends to rotate about an axis perpendicular to the N-O bond. ESR measurements were carried out at both 9 and 35 GHz and at temperatures ranging from 30 to 30 °C. Rather different results were obtained with the two spin labels, largely as a result of the different axes of rotation. Because the rotation rates were very slow, ESR spectra appeared as powder patterns rather than isotropic spectra and special methods were needed to extract the motional data. 

Robinson, A. J., Richards, W. G., Thomas, P. J. and Hann, M. M. (1995). Behavior of cholesterol and its effect on head group and chain conformations in lipid bilayers a molecular dynamics study, Biophys. J., 68, 164-170. 

Chiu, S.W., Jakobsson, E., Mashl, R.J., Scott, H.L. Cholesterol-induced modifications in lipid bilayers a simulation study. Biophys. J. 2002, 83, 1842-53. 

Effect of Cholesterol on Location of Organic Molecules in Lipid Bilayers An Infrared Spectroscopic Study... 

An aliphatic ketone (9-heptadecanone) and two keto derivatives of stearic acid (as potassium salts) containing a ketone functionality either at position 5 or 12 were incorporated into bilayers of the phospholipid l,2-dihexadecyl-sn-glycero-3-phosphocholine. Infrared spectra of these mixtures were measured as a function of temperature and amount of added cholesterol. It was found that the presence of cholesterol in these bilayers induces changes in the location of the guest ketone and that these changes are dependent on both temperature and cholesterol concentration. It is also demonstrated that, in the gel phase, the presence of cholesterol induces larger intersheadgroup separations and, therefore, water penetrates deeper into the lipid bilayer. 

From the data presented here several conclusions may be reached regarding the effect of cholesterol on lipid bilayers. It is shown that, even if the presence of cholesterol in bilayers serves to moderate temperature-induced changes, its ability to affect the location of solubilized molecules is highly temperature dependent We have also shown, in accord with previous work (11), that the presence of cholesterol in the gel phase results in a larger separation between the lipid polar groups and this in turn allows water to penetrate into the lipid hydrophobic core. 

Cholesterol - an essential component of mammalian cells - is important for the fluidity of membranes. With a single hydroxy group, cholesterol is only weakly am-phipathic. This can lead to its specific orientation within the phospholipid structure. Its influence on membrane fluidity has been studied most extensively in erythrocytes. It was found that increasing the cholesterol content restricts molecular motion in the hydrophobic portion of the membrane lipid bilayer. As the cholesterol content of membranes changes with age, this may affect drug transport and hence drug treatment. In lipid bilayers, there is an upper limit to the amount of cholesterol that can be taken up. The solubility limit has been determined by X-ray diffraction and is... 

The third class of lipids found in stratum corneum extracts is represented by cholesterol and cholesteryl esters. The actual role of cholesterol remains enigmatic, and no clear reason for its role in the barrier function has been proposed so far. However, it is possible that contrary to what is the role in cell membranes where cholesterol increases close packing of phospholipids, it can act as kind of a detergent in lipid bilayers of long-chain, saturated lipids.30,31 This would allow some fraction of the barrier to be in a liquid crystalline state, hence water permeable in spite of the fact that not only ceramides, but also fatty acids found in the barrier are saturated, long-chain species.28,32... 

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. 

Vibrational spectroscopy shows that inclusion of cholesterol in phospholipid bilayers tends to decrease the fluidity of the hydrophobic region above the main transition point Tm and to increase it below Tm. The presence of cholesterol in DPPC or DMPC muti-layered vesicles does not affect the transition point but simply broadens the transition by decreasing the CH2-stretching wavenumber in the liquid crystalline phase and by increasing it in the gel-like phase (Lippert and Peticolas, 1971 Spiker and Levin, 1976 Casal and Mantsch, 1984). There is also evidence that lipid-cholesterol interaction increases the amount of bound water in the headgroups (Levin et al., 1985). 

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. 

It is of interest not only to perforate vesicle membranes but also to destroy them after they have served their purpose as transport vehicles, in particular for DNA. Natural vesicles, so-called endosomes, contain about 50% cholesterol. The disruption of such cholesterol-containing lipid bilayers by Triton XI00 or sodium deoxycholate, examples of artificial and natural detergents, results in a leaky membrane at low concentration and in a catastrophic rupture process above the cmc of the amphiphiles. Vesicles made of fluid phospholipid bilayers devoid of cholesterol showed only leakiness under the same conditions. Amphiphiles with a carboxylate end group and a very bulky hydrophobic end (e.g., with two tert. butyl groups) disrupt membranes at pH 5 and have no effect above pH 7 (harpoons). For an example, see Figure 6.5.3. 

Natural vesicles, in particular endosomes for the fransport of proteins and nucleotides through cell membranes, contain about 50 mol% cholesterol in a bilayer where the lipids closely resemble the mixtures foimd in egg lecithins. Typ-... 

Several models for the structure of polyene—sterol pores in lipid bilayers have been presented [154,249-252]. They generally involve hydrophobic interaction between cholesterol and the unsaturated region of the polyene antibiotic, with possible hydrogen bond formation between the hydroxyl group of the sterol and the carbonyl group of the polyene ring. 

N. Chatteijee and H. Brockerhoff, Evidence for Stereospecific Phospholipid-Cholesterol Interaction in Lipid Bilayers, Biochim. Biophys. Acta 511, 116-119 (1978). 

DSC has also been used to investigate membrane associated cholesterol esters. Cholesterol esters have a very low solubility in lipid bilayers and are not normally found associated with biomembranes. Cholesterol esters, however, are found in substantial amounts in atherosclerotic lesions. 

Biological membranes are made of lipid bUayers. The most satisfactory model for the arrangement of phospholipids, proteins, and cholesterol in plant and animal membranes is the fluid-mosaic model proposed in 1972 by S. J. Singer and G. Nicolson. The term mosaic signifies that the various components in the membrane coexist side by side, as discrete units, rather than combining to form new molecules or ions. Fluid signifies that the same sort of fluidity exists in membranes that we have already seen in lipid bilayers. Furthermore, the protein components of membranes float in the bilayer and can move laterally along the plane of the membrane. 

Cholesterol is found abundantly in animal plasma membranes, and the specific interaction of cholesterol with lipid bilayers in an important biological topic. It appears that cholesterol derivatives interact specifically with ammonium bilayers as well. In the hydrolysis of phenyl esters, cholest-Im showed an especially high reactivity when bound to the 2C] 2N 2C bilayer(18). Cholic acid-derived nucleophiles showed normal reactivity patterns, as may be expected from the fact that cholic acid tends to disintegrate the phospholipid bilayer. 

Maeba, R and Ueta, N (2003) Ethanolamine plasmalogens prevent the oxidation of cholesterol by reducing the oxidizability of cholesterol in phospholipid bilayers. J Lipid Res, 44, 164-171. 

The inclusion of cholesterol disturbs the crystalline structure of the gel phase, and the phospholipid chains are more mobile than in its absence. This prevents the crystallization of the hydrocarbon chains into the rigid crystalline gel phase. In the more fluid liquid crystalline phase, the rigid cholesterol molecules restrict the movement of the hydrocarbon chains. In consequence, the addition of cholesterol to lipid bilayers or lamellar mesophases gradually diminishes the gel-liquid crystal transition temperature and the enthalpy and broadens the DSC transition peak [72,73]. No transition can be detected by DSC at 50% cholesterol [73,74] (curve/of Fig. 7), which is the maximum concentration of cholesterol that can be incorporated before phase separation. However, laser Raman spectroscopic studies show that a noncooperative transition occurs over a very wide temperature range [75]. 

Matylevich, N. P. Eluctuation accumulations of cholesterol molecules in lipid bilayer determine substance distribution between the membrane and water phases. Biofizika 1986, 31, 714—716 Chem. Abstr. 1986, 105, 130214. 

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