Vitamin E Does Not Disturb Polyunsaturated Fatty Acid Lipid Domains

The function of vitamin E in biomembranes remains a prominent topic of discussion. As its limitations as an antioxidant persist and novel functions are discovered, our understanding of the role of vitamin E becomes increasingly enigmatic. As a group of lipophilic molecules (tocopherols and tocotrienols), vitamin E has been shown to influence the properties of its host membrane, and a wealth of research has connected vitamin E to polyunsaturated fatty acid (PUFA) lipids. Here, we use contrast-matched small-angle neutron scattering and differential scanning calorimetry to integrate these fields by examining the influence of vitamin E on lipid domain stability in PUFA-based lipid mixtures. The influence of α-tocopherol, γ-tocopherol, and α-tocopherylquinone on the lateral organization of a 1:1 lipid mixture of saturated distearoylphosphatidylcholine (DSPC) and polyunsaturated palmitoyl-linoleoylphosphatidylcholine (PLiPC) with cholesterol provides a complement to our growing understanding of the influence of tocopherol on lipid phases. Characterization of domain melting suggests a slight depression in the transition temperature and a decrease in transition cooperativity. Tocopherol concentrations that are an order of magnitude higher than anticipated physiological concentrations (2 mol percent) do not significantly perturb lipid domains; however, addition of 10 mol percent is able to destabilize domains and promote lipid mixing. In contrast to this behavior, increasing concentrations of the oxidized product of α-tocopherol (α-tocopherylquinone) induces a proportional increase in domain stabilization. We speculate how the contrasting effect of the oxidized product may supplement the antioxidant response of vitamin E.