Atomistic Simulations of Small Molecule Permeation Through Lamellar/Nonlamellar Lipid Membranes

Abstract

Passive permeation through biological membranes is an important mechanism for transporting molecules and regulating the cell's content. In vivo membranes typically consist of mixtures of lamellar and nonlamellar lipids. Lamellar lipids are characterized by their tendency to form lamellar bilayer phases, which are predominant in biology. Nonlamellar lipids, when isolated, instead form non-bilayer structures such as inverse hexagonal phases. While mixed lamellar/nonlamellar lipid membranes tend to adopt the ubiquitous bilayer structure, the presence of nonlamellar lipids is known to have profound effects on key membrane properties, such as the lateral pressure profile and associated elastic constants. In this study, we examine the effect of changing the lamellar vs. nonlamellar lipid composition on the transmembrane passive permeation process. In particular, we investigate a series of small molecules including water, carbon dioxide, ammonia, and fluoromethane. We utilize atomistic molecular dynamics simulations and the z-constraint method, to obtain transfer free energy profiles, as well as the diffusion and permeation coefficients; these properties are not readily accessible by experiment. Our preliminary results indicate that the addition of nonlamellar lipids enhances the transfer of permeants through the interfacial lipid head region, while it hinders it in the hydrocarbon tails core.