Simulating Pores in Saturated Phosphatidylcholine Lipid Bilayers

Abstract

Lipid bilayers form the basic structure of cellular membranes. There is a large degree of diversity in the structure and composition of biological membranes. While one of the most important functions of membranes is to prohibit polar molecules from crossing the membrane, pore formation is crucial in a number of biological processes. We have used atomistic simulations to investigate the thermodynamics and kinetics of pore formation and dissipation in three saturated phosphatidylcholine bilayers, DLPC, DMPC, and DPPC. Pore formation has a large free energy cost, which increases as the tails length increases: 16 kJ/mol (DLPC), 40 kJ/mol (DMPC), and 80 kJ/mol (DPPC). We find that pore formation has a large unfavorable entropic contribution, possibly due to the constriction of water within the pore. The large unfavorable entropic contribution is compensated by a favorable enthalpic contribution to pore formation. Once formed, pores in the shorter lipid bilayers are larger and more stable than pores in bilayers with longer lipids. These results have broad implications on biological processes involving pore formation, such as lipid flip-flop, antimicrobial peptides, and cell penetrating peptides.