Lipid conformation, cholesterol effects

Lipids and membranes. Interchain interactions and melting behavior of the lipid aliphatic chains effects of chemical perturbants (e.g., cholesterol) and proteins on melting behavior lipid head-group conformation... 

Yeagle, P. L. Hutton, W. C. Huang, C.-H. Martin, R. B., Headgroup conformation and lipid-cholesterol association in phosphatidylcholine vesicles A 31P 1H nuclear Over-hauser effect study, Proc. Natl. Acad. Sci. 72, 3477-3481 (1975). 

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. 

Hopanoids (the most common organic natural product on earth) must have been involved in the evolution of the biomembrane itself. All known membranes contain terpene derivatives, such as cholesterol or carotenoids, which belong to, or can be derived from, hopanoids. However, we still do not know their biological function. Their most commonly proposed mechanism is to regulate membrane fluidity. Another obvious effect is their influence on the lipid bilayer (or monolayer in the case of archaebacteria) curvature. The different types of hopanoids occurring will certainly favour the relative stability of either the planar or of the intrinsically curved membrane conformation. The ether lipids of archaebacteria, which are hopanoid derivatives, forming curved bilayers as discussed above, therefore provide evidence for cubosomes as the first organised form of life. 

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. 

For the description of the chain-melting phase transition of pure lipid bilayer membranes the microscopic model of Pink and collaborators has been adopted. This model takes into account the acyl-chain conformational statistics and the van der Waals interaction between various conformers in a detailed way, while the excluded volume effect is accounted for by assigning each lipid chain to a site in a triangular lattice. The acyl chain conformations are represented by ten single chain states a , each described by a cross-sectional area A , an internal energy Ea and an internal degeneracy Da- The second membrane component is assumed to be a stiff, hydrophobically smooth molecule with no internal degrees of freedom and a cross-sectional area Ac- The model parameters will be chosen so that the mixture display the properties of the DPPC-cholesterol bilayer system for small concentrations of cholesterol [3]. The impurity will hereafter be called cholesterol . 

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