Atomistic Simulation of Pore Formation in Lipid Bilayers in the Presence of Dimethylsulfoxide: Further Evidence for Entropic Driven Pore Formation

In a recent study, Moldovan et al [1] have demonstrated that in the presence of 11.3 mol% dimethylsulfoxide (DMSO) a pore can nucleate and grow spontaneously in a lipid bilayer even in the absence of an externally applied stresses or electric field. The authors rationalized the spontaneous pore nucleation, in the absence of any external driving force, by considering the combined effect of the entropy of pore shape fluctuation and the significant decrease of the bilayer line tension in the presence of DMSO. Building on the classical nucleation theory developed three decades ago by Lister [2] the authors propose a new formulation for the bilayer free energy that incorporates the pore shape configurational entropy. According to this study, in the presence of DMSO, the pore nucleates spontaneously and grows provided the bilayer line tension decreases below a threshold value, λ. In this study we report our recent simulation results on the effect of DMSO concentration on both bilayer line tension and bilayer structural stability with respect to pore nucleation. The lipid bilayer systems investigated in this study by molecular dynamics (MD) consists of 96 molecules (48 in each leaflet) of dimyristoylphosphatidylcholine (DMPC) immersed in DMSO-water solutions at various concentrations. In all MD simulations reported the bilayer systems were followed over 100 ns. Our simulations results indicate the existence of a critical DMSO concentration below which there are no pores nucleated in the lipid bilayers. Our findings corroborate and complement the entropy-based pore nucleation model proposed earlier by Moldovan et al. [1].