Membrane Organization of Vitamin E is Sensitive to Lipid Unsaturation

Abstract

Vitamin E (α-tocopherol) has long been known as the major antioxidant in biological membranes. However, there remain many structurally related questions. Details of the molecular organization of α-tocopherol in membranes, for instance, lack the precision to address whether the vitamin has preferential affinity for unsaturated lipids in support of its role as an antioxidant. To observe how α-tocopherol interacts with unsaturated phospholipids, we determine, from one-dimensional neutron scattering length density profiles, the depth of deuterated analogs in phosphatidylcholine (PC) bilayers. The profiles obtained with α-[5-2H3]tocopherol and α-[9′-2H2]tocopherol in 1,2-dioloeylphosphatidylcholine (18:1-18:1PC) bilayers place the centers of mass of the labels 13 and 0 A, respectively, from the bilayer center. They are consistent with the vitamin molecule sitting upright in the bilayer so that the hydroxyl group on the chromanol is near the aqueous interface and a highly disordered sidechain extends towards the middle of the membrane. The profile obtained for α-[5-2H3]tocopherol in 1-palmitoyl-2-oleeylphosphatidylcholine (16:0-18:1PC) reveals that, in contrast, the center of mass of the label sits 10 A higher than in 18:1-18:1PC. A remarkable sensitivity upon membrane unsaturation for the depth of penetration of vitamin E is implied, and we are currently using solid state 2H NMR and MD simulations to provide a detailed view of dynamical organization.