Transmembrane Potential enhances Direct Translocation of Cell-Penetrating Peptides
作者单位：State Key Laboratory of Organic-Inorganic CompositesBeijing University of Chemical Technology State Key Laboratory of Heavy Oil ProcessingCenter for Bioengineering and BiotechnologyChina University of Petroleum (East China) International Research Center for Soft MatterBeijing University of Chemical Technology
会议名称：《中国化学会2016年软物质理论计算与模拟会议》
会议日期：2016年
学科分类：0710[理学-生物学] 07[理学] 071009[理学-细胞生物学]
基 金：supported by National Natural Science Foundation of China(Nos.21276007 and 91434204)
关 键 词：Cell-penetrating peptides membrane membrane potential translocation
摘 要：Cell-penetrating peptides（CPPs） are shown experimentally to be capable of entering cells in an energy-independent pathway of direct translocation,which is complementary to endocytosis and featured by the rapid uptake,making CPPs a fascinating drug delivery agent.The mechanisms underlying the direct penetration of CPPs,however,are still open challenges.In this work,both direct molecular dynamics simulations and free energy calculations demonstrate that the transmembrane potential due to the ion concentration difference between the intracellular and extracellular regions and local membrane potential enhancement due to CPP adsorption play essential roles in the direct translocation of CPPs.In particular,our simulations show that the local membrane potential enhancement caused by highly charged CPP structures and by high CPP density on the membranes cooperatively promote the formation of a membrane pore,through which the peptides could penetrate into the membrane hole from one end with a chain-like structure.These findings not only interpret the mechanism of CPP penetration across membrane,but also demonstrate the importance of transmembrane potential for many cell activities.