Polar groups, cholesterol effects

Film penetration studies show unequivocally that lecithin-cholesterol mixtures containing from 0 to 50 mole % cholesterol and lecithin—lactoside mixtures containing from 0 to 80 mole % Ci6-dihydroceramide lactoside have the same effect as pure lecithin. This suggests the presence of a lipid complex in which lecithin prevents the interaction of the cholesterol or ceramide lactoside with globulin. Over these ranges of composition the lipid film would consist of a mixture of the lecithin-cholesterol or the lecithin-lactoside complex with excess lecithin. One may picture two models in which the protein contact is restricted to molecules of lecithin. In one, individual polar groups of the protein interact with the excess lecithin molecules as well as with the lecithin portions of the complex. In the other model, the protein as a whole interacts with the lecithin sites of polymeric lipid structures. The latter, which could be referred to as surface micelles (I), are visualized also through the term "mono-... 

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 can modify both the hydrophobic attraction between lipid hydrocarbon chains and electrostatic interactions between lipid polar groups. The influence it has on the location of 9HP reflects this dual effect At low temperature, the "spacer" effect of cholesterol allows the ketone to gain access directly to the lipid-water interface. At high temperatures, a more disordered hydrocarbon core favors the solubilization of the guest molecule. 

A major effect of cholesterol on the conformation of apoE was revealed by comparing the conformation on DMPC discs, on HDLc, and on spherical artificial microemulsion particles by circular dichroism (Mims et ai, 1990). Conformational differences of apoE on different types of particles also were demonstrated using NMR to probe lysyl microenvironments. When the apoE lysyl residues were labeled by reductive methylation with [ C]formaldehyde to allow detection, the lysyl microenvironments manifested dramatic differences on a discoidal particle compared to spherical particles (S. Lund-Katz et aL, 1993). On spherical particles, two lysine microenvironments were observed, but on discoidal particles eight peaks were observed (apoE has 12 lysyl residues). These results indicate that apoE structure differs significantly on the two lipid surfaces. In a systematic study of the effect of the particle lipid composition on the conformation of apoE, conformation was shown to be affected by a number of parameters (Mims et ai, 1990). The a-helical content was lower when apoE was bound to a spherical particle compared to a discoidal particle. It was concluded that this probably reflects the different ways in which the amphipathic helices interact with phospholipid on the two particles. With discoidal particles the interaction is primarily with phospholipid acyl side chains, whereas with spherical particles the interaction is with polar phospholipid head groups. In addition, the conformation of apoE was influenced by the diameter of the microemulsion particle and possibly by the order/ disorder of the lipid components. 

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