Vitamin E Differentially Destabilizes Bilayer Structure of Docosahexaenoic and Oleic-Acid Containing Model Membranes

Abstract

Vitamin E (α-tocopherol) is a lipid-soluble antioxidant that has a primary role of protecting polyunsaturated phospholipids from oxidation in membranes. Whether there is preferential interaction between α-tocopherol and polyunsaturated phospholipids to optimize this function has been a longstanding question. Here we compare the effect of α-tocopherol on the molecular organization of polyunsaturated 1-palmitoyl-2-docosahexaenoyl-sn-glycerophosphatidylethanolamine (16:0-22:6PE, PDPE) and monounsaturated 1-palmitoyl-2-oleoyl-sn-glycerophosphatidylethanolamine (16:0-18:1PE, POPE) in mixtures with sphingomyelin (SM). By solid-state 2H NMR spectroscopy, we directly observed POPE-d31 and PDPE-d31 (analogs of POPE and PDPE with a perdeuterated sn-1 chain) in the mixed membranes. In supplementary X-ray diffraction experiments, we further probed membrane architecture. At higher temperatures (>20 °C), the spectra observed for POPE-d31 in POPE/SM/α-tocopherol (2:2:1 mol) and for PDPE-d31 in PDPE/SM/α-tocopherol (2:2:1 mol) consist of a superposition of two spectral components that we ascribe to α-tocopherol promoting a transition from lamellar (Lα) to inverted hexagonal (HII) phase. This interpretation is confirmed by X-ray diffraction data. Analysis of depaked spectra shows that the amount of HII phase increases with temperature. The increase ranges from 7 to 28% between 31 and 55 °C for POPE-d31, while for PDPE-d31 the increase is less and ranges from 6 to 20% over the same temperature range. A more modest increase in acyl chain order is also seen for PDPE-d31 (3%) than POPE-d31 (8%) remaining in the Lα phase (37 °C). The molecular origin of the differential in bilayer stability between the two mixed membranes will be discussed in terms of the greater disorder of PDPE and its ability to accommodate α-tocopherol.