Does vitamin E behave like cholesterol? An examination of vitamin E's effects on phospholipid membrane structure and...

Vitamin E (VE) has historically been described as an antioxidant and its roles in radical species scavenging and nutrition are well studied. VE has been proposed to have secondary roles within the membrane but these roles are not as well characterized, with contradictory results emerging throughout the literature. Due to similar structural motifs, comparisons between VE and cholesterol (CHO), another membrane component, have been commonly made. Despite these comparisons showing that phospholipid-CHO and phospholipid-VE interactions may behave similarly, VE's potential influence on phospholipid flip-flop specifically is not as well studied when compared with CHO's influence. Here, we show through the use of sum-frequency vibrational spectroscopy that VE at both biological (0.5-1.5 mol %) and supraphysiological (2.5-5 mol %) concentrations shows similar characteristics to that of CHO in its ability to induce alkyl chain ordering of phospholipids within planar supported lipid bilayers of the saturated lipid 1,2-dipalmitoyl-sn-glycero-3-phosphocholine. In addition to chain ordering, the introduction of VE accelerates phospholipid flip-flop by approximately three times (0.5-2.5 mol %) with rates approaching an order-of-magnitude increase (5 mol %) at high VE content. The increase in phospholipid flip-flop rates is attributed to the decrease in the molar compression modulus of the membrane. These results suggest that VE influences the ordering and compressibility of the membrane similar to CHO.