Molecular Dynamics Simulation Studies of Interaction of Amphiphilic Molecules with Lipid Bilayers

Abstract

We use molecular dynamics simulations to investigate the behavior of various amphiphilic molecules in aqueous solutions in the presence of vitamin E or lipid bilayers. Our research studies focus on two molecular systems. First, we investigate the effect of DMSO on structural properties of DMPC bilayers and calculate bilayers permeability coefficients for both water and DMSO molecules at low DMSO concentration. The simulations show that the increase of DMSO concentration in solution leads to an increase of the permeability of water through the bilayers. The permeability increase might explain the unusual ability of DMSO, even at relatively low concentrations, to allow fast relaxation of osmotic pressure imbalance present during cryopreservation protocols. The second part of our research aims at the development of a molecular-level understanding of solubilization of vitamin E by bile salts and its adsorption and positioning into cell membranes. Specifically, in a sequence of MD simulations, we investigate the aggregation behavior and interaction of cholate (CHD) and glycocholate (GCH) with oleic acid and vitamin E and adsorption, positioning, and aggregation of vitamin E molecules inside a DMPC lipid bilayer. The simulations show that at concentrations above critical micelle concentration the bile salt molecules aggregate spontaneously into small ablate micelles in just a few nanoseconds. The oblate shape is favored by bile salts unique molecular structure. The study of interaction of bile salts with oleic acid show that oleic acid molecules are solubilized spontaneously into preformed bile salt micelles. The MD study of interaction of bile salts with vitamin E show that preformed bile salt micelles are spontaneously adsorbed at the vitamin E-water interface; adsorption process that leads to important changes of interfacial energy, surface tension, and interface structure. In addition, our MD simulations demonstrate that a-tocopherol incorporates spontaneously into DMPC lipid bilayers and accumulates in a relatively narrow region, just below the membrane-water interface. This is of great significance because even if its concentration in membranes is relatively low, the spatial confinement of a-tocopherol inside the bilayer greatly enhances its concentration in this vital region, thus increasing their importance for in vivo biological activities including oxidative stress defense.