A Role for Lipid-Lipid Interactions in Vitamin E's Function as a Membrane Antioxidant

Abstract

Vitamin E (α-tocopherol) is the principle lipid soluble antioxidant in cell membranes. Its purpose is to protect membrane lipids from oxidative damage. Whether unequal affinity for different lipids optimizes the proximity of vitamin E to polyunsaturated phospholipids, the lipid species most susceptible to oxidation, is the question that we address with MD simulations on lipid bilayers. Our studies suggest cholesterol, ubiquitous in the cell membranes of animals, excludes vitamin E from saturated raft-like domains enriched in the sterol. Preferential affinity for polyunsaturated phospholipids is not indicated - vitamin E, like polyunsaturated phospholipids, is pushed towards non-raft regions depleted in cholesterol. The binding energy measured for vitamin E in umbrella sampling AA (all-atom) simulations is greater for SM (sphingomyelin) than PDPC (1-palmitoyl-2-docosahexaenoyl-sn-glycero-3-phosphocholine). Adding cholesterol to SM eliminates the differential in binding energy. CG (coarse-grained) simulations run on PDPC/SM/cholesterol mixtures in the presence of vitamin E indicate the vitamin locates at the boundary between SM-rich/sterol-rich (raft-like) and PDPC-rich/sterol-poor (non-raft) domains. CG simulations run on mixtures replacing PDPC by DDPC (1,2-didocosahexanoyl-sn-glycero-3-phosphocholine) will reveal details of the molecular interactions of vitamin E at the distinct boundary between raft-like and non-raft domains that forms with the di-polyunsaturated phospholipid. The results of these studies will be presented.