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.

Transformation of Lipid Vesicles into Micelles by Adding Nonionic Surfactants: Elucidating the Structural Pathway and the Intermediate Structures.

The phospholipid lecithin (L) and the nonionic surfactant Tween 80 (T) are used together in various contexts, including in drug delivery and oil spill remediation. There is hence a need to elucidate the nanostructures in LT mixtures, which is the focus of this paper. We study these mixtures using cryogenic transmission electron microscopy (cryo-TEM), coupled with dynamic light scattering and small-angle neutron scattering. As the concentration of Tween 80 is increased, the vesicles formed by lecithin are transformed into spherical micelles. We identify bicelles (i.e., disc-like micelles) as well as cylindrical micelles as the key stable nanostructures formed at intermediate L/T ratios. The bicelles have diameters ∼13-26 nm, and the bicelle size decreases as the Tween 80 content increases. We propose that the lecithin lipids form the body of the discs, while the Tween 80 surfactants occupy the rims. This hypothesis is consistent with geometric arguments because lecithin is double-tailed and favors minimal curvature, whereas the single-tailed Tween 80 molecules prefer curved interfaces. In the case of cylindrical micelles, cryo-TEM reveals that the micelles are short (length < 22 nm) and flexible. We are able to directly visualize the microstructure of the aggregates formed by lecithin-Tween 80 mixtures, thereby enhancing the understanding of morphological changes in the lecithin-Tween 80 system.

The antioxidant vitamin E as a membrane raft modulator: Tocopherols do not abolish lipid domains.

The antioxidant vitamin E is a commonly used vitamin supplement. Although the multi-billion dollar vitamin and nutritional supplement industry encourages the use of vitamin E, there is very little evidence supporting its actual health benefits. Moreover, vitamin E is now marketed as a lipid raft destabilizing anti-cancer agent, in addition to its antioxidant behaviour. Here, we studied the influence of vitamin E and some of its vitamers on membrane raft stability using phase separating unilamellar lipid vesicles in conjunction with small-angle scattering techniques and fluorescence microscopy. We find that lipid phase behaviour remains unperturbed well beyond physiological concentrations of vitamin E (up to a mole fraction of 0.10). Our results are consistent with a proposed line active role of vitamin E at the domain boundary. We discuss the implications of these findings as they pertain to lipid raft modification in native membranes, and propose a new hypothesis for the antioxidant mechanism of vitamin E.