All–atom molecular dynamics simulation of the combined effects of different phospholipids and cholesterol contents on electroporation

Abstract

The electroporation mechanism could be related to the composition of the plasma membrane, and the combined effect of different phospholipids molecules and cholesterol contents on electroporation is rarely studied and concluded. In this paper, we applied all-atom molecular dynamics (MD) simulation to study the effects of phospholipids and cholesterol contents on bilayer membrane electroporation. The palmitoyl-oleoyl-phosphatidylcholine (POPC) model, palmitoyl-oleoyl-phosphatidylethanolamine (POPE) model and 1:1 mixed model of POPC and POPE called PEPC were three basic models. An electric field of 0.45 V/nm was applied to nine models including three basic models with cholesterol contents of 0%, 24%, and 40%. The interfacial water molecules moved under the electric field, and once the first water bridge formed, the rest of the water molecules would dramatically flood into the membrane. The simulation showed that a rapid rise in the Z component of the average dipole moment of interfacial water (Z-DM) indicated the occurrence of electroporation, and the same increment of Z-DM represented the similar change in the size of water bridge. With the same cholesterol content, the formation of the first water bridge was the most rapid in POPC model regarding the average electroporation time (tep), and the average tep of the PEPC model was close to that of the POPE model. We speculate that the difference in membrane thickness and initial hydrogen bonds of interfacial water affecting the average tep among different membrane composition. Our results reveal the influence of membrane composition on electroporation mechanism at the molecular level.