Vitamin E Promotes the Inverse Hexagonal Phase Providing Insights on Lipid Packing Stresses: Studies by SAXS and 2H NMR

Vitamin E protects membrane lipids from oxidation. How vitamin E partitions within a membrane and whether it preferentially interacts with polyunsaturated lipids are long-standing questions. Polyunsaturated fatty acids (PUFA) preferentially incorporate into phosphatidylethanolamine (PE) lipids, which have a tendency to form the inverse hexagonal (H II) phase. We present small-angle X-ray scattering (SAXS) and solid state 2H NMR data that illustrate vitamin E promotes the transition to H II phase in PE lipids. It has been established that hydrophobic molecules, such as dodecane, promote the H II phase in PE lipids by packing in the hydrophobic interior and so relieving the extensive stress. The hydrophilic hydroxyl head group on vitamin E, in contrast, is anchored near the aqueous surface while the phytanyl chain extends into the hydrophobic region. Based on analysis of our data we then reason that vitamin E promotes the H II phase by a novel mechanism, instead relieving the compressive stress. These observations provide a deeper understanding of lipid packing stress and potentially give insight into a structural role for vitamin E in its function to protect polyunsaturated lipids that are most vulnerable to oxidative attack