Comparison of Activation Energy and Pore Dynamics in Liquid and Gel Phases of Electroporated Lipid Bilayers using Temperature Dependent MD Simulations

The molecular level understanding of electroporation has been studied by few research groups [1, 2, 3] over the last decade. We have performed molecular dynamics simulation(MDS) of electroporation at different temperatures to find activation energy as well as pore dynamics in the gel and liquid phases of POPC and DPPC lipid bilayers.The MDS of bilayers were performed using NAMD, the Particle mesh Ewald(PME) method, the all-atom CHARMM force field and an integrated time-step of 2 fs.The bilayers were composed of 256 lipids which were solvated with TIP3 water molecules with a low KCl concentration. The MD simulations were performed in temperature range from 250 K to 350 K with varying electric fields (0.02 to 1 V/nm).A plot of pore initiation rate as a function of inverse temperature showed Arrhenius type behaviour. The activation energy was determined to be 25.5 and 21.5 kJ/mol for the liquid phase of POPC and DPPC lipids respectively for an electric field of 0.3 V/nm, and reduces at higher fields. The activation energy in the gel phase of POPC increases to 28.8 kJ/mol at the same field. The pore closing time after the field is switched off was found to be longer in the gel phase than in the liquid phase. Remarkably, pores of radii ∼0.7nm in the gel phase of POPC did not close even after 50ns, whereas they close completely within 10ns in the liquid phase.[1]M Tarek, Biophysical. J., 88 (2005) 4045-4053.[2]PT Vernier, MJ Ziegler, Y Sun, WV Chang, MA Gundersen and DP Tieleman, J. Am. Chem. Soc., 128 (2006) 6288-6289.[3]WFD Bennett, N Sapay and DP Tieleman, Biophysical. J., 106 (2014) 210-219.