Molecular Dynamics Simulation Studies of Pore Formation in Lipid Bilayers in the Presence of Dimethylsulfoxide

Abstract

We report in this work our observations from detailed atomistic investigations of the interactions between solutions containing 11.3 mol% of dimethylsulfoxide (DMSO) and three fully hydrated bilayers of lipid molecules, (BLMs). The BLMs considered were: dipalmitoyl-phosphatidylcholine (DPPC), palmitoyloleoyl-phosphatidylcholine (POPC) and dimyristoylphosphatidylcholine (DMPC); all in the fluid phase and under equilibrium conditions at 323K and 298K, respectively. All of our simulations were performed over 100 ns total simulation time and in the absence of any externally applied stress to the membranes. In all three systems investigated, in the presence of DMSO, we observed that small hydrophobic pores start to open across the membranes at various times during the simulations ranging from 10 ns for the DMPC, 45ns for POPC to 50ns for DPPC membrane. By carefully analyzing the membranes structures we concluded that hydrophobic pores open and close continuously during the simulation beyond the above mentioned time marks. Interestingly, as there is no external stress applied to the membranes these hydrophobic pores are presumably nucleated by thermal fluctuations. In all three systems we also observe that after some time after the first hydrophobic pore nucleation the pore starts to grow and transforms into a hydrophilic pore which continue to grow at an even higher rate. Our MD simulation studies of various BLMs indicate that the presence of DMSO may lower the pore edge line tension leading to pore nucleation and growth due to only thermal fluctuations.