Shape Pairing of Cholesterol with Oxidized Phospholipid Species in Lipid Bilayers

Abstract

We show that (1) cholesterol protects bilayers from disruption caused by lipid oxidation by sequestering conical shaped oxidized lipid species (PZPC) away from phospholipid, because cholesterol and the oxidized lipid have complimentary shapes and (2) mixtures of cholesterol and oxidized lipids can self-assemble into bilayers much like lysolipid-cholesterol mixtures. The evidence for bilayer protection comes from MD simulations and DLS measurements. Bilayers containing high amounts of PZPC become porous, unless cholesterol is also present. The protective effect of cholesterol from oxidized lipids has been observed previously using EPR and electron microscopy imaging of vesicles. The evidence for the pairing of cholesterol and PZPC comes from the 2-D density plots and different thickness regimes from simulations. The density plots show that these two molecules co-localize in bilayers. Cholesterol-PZPC rich regions are thinner than phospholipid-rich regions in the same bilayer. We further demonstrate the affinity of PZPC and cholesterol in self-assembly simulations, where we show that cholesterol-oxidized lipid mixtures can form bilayers without phospholipids at specific concentrations, reminiscent of lysolipid-cholesterol mixtures. The additivity of the packing parameters of cholesterol and PZPC explains their cohabitation in a planar bilayer.View Large Image | View Hi-Res Image | Download PowerPoint Slide