Guo Fei, Wang Ji, Zhou Jiong, Qian Kun, Qu Hongchun, Liu Ping, Zhai Shidong
Institute of Ecological Safety, Chongqing University of Posts and Telecommunications Chongqing 400065 China
RSC Adv. 2022 Aug 30;12(38):24491-24500. doi: 10.1039/d2ra03895a.
The electroporation mechanism could be related to the composition of the plasma membrane, and the combined effect of different phospholipid molecules and cholesterol content on electroporation has rarely been studied nor conclusions drawn. In this paper, we applied all-atom molecular dynamics (MD) simulations to study the effects of phospholipids and cholesterol content on bilayer membrane electroporation. The palmitoyloleoylphosphatidylcholine (POPC) model, palmitoyloleoylphosphatidylethanolamine (POPE) model, and a 1 : 1 mixed model of POPC and POPE called PEPC, were the three basic models used. An electric field of 0.45 V nm was applied to nine models, which were the three basic models, each with three different cholesterol content values 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 -component of the average dipole moment of the interfacial water molecules (-DM) indicated the occurrence of electroporation, and the same increment of -DM represented a similar change in the size of the water bridge. With the same cholesterol content, the formation of the first water bridge was the most rapid in the POPC model, regarding the average electroporation time ( ), and the average of the PEPC model was close to that of the POPE model. We speculate that the differences in membrane thickness and initial number of hydrogen bonds of the interfacial water molecules affect the average for different membrane compositions. Our results reveal the influence of membrane composition on the electroporation mechanism at the molecular level.
电穿孔机制可能与质膜的组成有关，不同磷脂分子和胆固醇含量对电穿孔的综合影响鲜有研究，也未得出结论。在本文中，我们应用全原子分子动力学（MD）模拟来研究磷脂和胆固醇含量对双层膜电穿孔的影响。使用的三个基本模型分别是棕榈酰油酰磷脂酰胆碱（POPC）模型、棕榈酰油酰磷脂酰乙醇胺（POPE）模型以及POPC和POPE的1:1混合模型（称为PEPC）。对九个模型施加了0.45 V/nm的电场，这九个模型是三个基本模型，每个基本模型又分别具有0%、24%和40%这三种不同的胆固醇含量值。界面水分子在电场作用下移动，一旦形成第一个水桥，其余水分子就会大量涌入膜内。模拟结果表明，界面水分子平均偶极矩的z分量（-DM）迅速上升表明发生了电穿孔，-DM的相同增量表示水桥大小的类似变化。在相同胆固醇含量下，就平均电穿孔时间（ ）而言，POPC模型中第一个水桥的形成最为迅速，PEPC模型的平均 与POPE模型相近。我们推测，膜厚度和界面水分子氢键初始数量的差异会影响不同膜组成的平均 。我们的结果揭示了膜组成在分子水平上对电穿孔机制的影响。
