Electropore Dynamics in Time-Dependent Electric Fields

Abstract

Experimental studies have shown that cell membranes can be permeabilized by exposure to nanosecond and subnanosecond electric pulses with megavolt-per-meter amplitudes [1,2]. For pulses in the low nanosecond and subnanosecond range, the rise time of the actual waveform delivered to a biological load is a significant percentage of the entire pulse duration, but experimental and modeling studies of the effects of varying the rise time are rare. Molecular dynamics (MD) simulations have contributed to our understanding of lipid bilayer electropermeabilization, and we show here that when time-varying external fields are introduced into MD, it becomes possible to modulate pore properties dynamically by sampling a large range of frequencies, fields, pulse shapes, and polarities with various charged and uncharged bilayer systems. This capability also enables the refinement of models of nanosecond pore formation by loosening the constraints of models with constant and idealized external perturbations. Results are compared to and, to the extent possible at this time, reconciled with existing mathematical models of electroporation, presenting a more unified and complete framework for future studies.1. Vernier, P. T., Y. Sun, and M. A. Gundersen. 2006. Nanoelectropulse-driven membrane perturbation and small molecule permeabilization. BMC Cell Biol. 7:37.2. S. Xiao, S. Guo, V. Nesin, R. Heller, and K. H. Schoenbach. 2011. Subnanosecond electric pulses cause membrane permeabilization and cell death. IEEE Trans. Biomed. Eng. 58:1239-1245.