Simulations of transient membrane behavior in cells subjected to a high-intensity ultrashort electric pulse

Abstract

A molecular dynamics (MD) scheme is combined with a distributed circuit model for a self-consistent analysis of the transient membrane response for cells subjected to an ultrashort (nanosecond) high-intensity (approximately 0.01-V/nm spatially averaged field) voltage pulse. The dynamical, stochastic, many-body aspects are treated at the molecular level by resorting to a course-grained representation of the membrane lipid molecules. Coupling the Smoluchowski equation to the distributed electrical model for current flow provides the time-dependent transmembrane fields for the MD simulations. A good match between the simulation results and available experimental data is obtained. Predictions include pore formation times of about 5-6 ns. It is also shown that the pore formation process would tend to begin from the anodic side of an electrically stressed membrane. Furthermore, the present simulations demonstrate that ions could facilitate pore formation. This could be of practical importance and have direct relevance to the recent observations of calcium release from the endoplasmic reticulum in cells subjected to such ultrashort, high-intensity pulses.

Long‐lasting plasma membrane permeabilization in mammalian cells by nanosecond pulsed electric field (nsPEF)

“…We found that even relatively low-amplitude nsPEF caused a profound and long-lived permeabilization of the plasma membrane. These data provided support to the theoretical models [Hu et al, 2005;Gowrishankar and Weaver, 2006;Smyth et al, 2006] and also suggested that other known nsPEF effects [Beebe et al, 2003a,b;Stacey et al, 2003;Pakhomov et al, 2004] may be mediated, at least in part, by the disruption of the barrier function of the plasma membrane.…”

“…At the same time, analytical models of nsPEF effect on cells [Foster, 2000;Joshi et al, 2002;Gowrishankar and Weaver, 2006;Kotnik and Miklavcic, 2006;Smyth et al, 2006] and numerical simulations [Tieleman, 2004;Hu et al, 2005;Tarek, 2005] suggested that the cell plasma membrane is not ''exempt'' from poration. Instead, the anticipated effect is formation of pores in large numbers, both in the plasma membrane and in the internal membranes of cell organs.…”

Nanosecond pulsed electric fields cause melanomas to self-destruct

“…Since heating is proportional to pulse duration and the square of the field strength, the much shorter pulses in the nanosecond range can have a higher field strength while delivering the same low level of thermal energy to the tissue. Here, we use a 20-fold higher field strength of 40 kV/cm and this generates structural changes in the plasma membrane that result in a smaller electrical barrier as well as higher voltage gradients across cellular organelles for the duration of the pulse [17]. A typical tumor cell nucleus measuring 10 μm in diameter will experience a voltage gradient of roughly 40 V across its diameter during each pulse.…”

High-Order Quadratures for the Solution of Scattering Problems in Two Dimensions

“…Molecular dynamics (MD) and micro-and macroscale modeling with field solvers and electrical circuit representations can be used profitably to create simulations for consistency checks and verification of proposed nanoelectropulse perturbation mechanisms, and to generate hypotheses for testing with available laboratory resources. In order to identify the molecular mechanisms operative on a nanosecond time scale during electroporation of phospholipid bilayers, for example, MD simulations of phospholipid bilayers in high electric fields can suggest details of electroporation kinetics and dynamics not directly accessible by experiment [30,31].…”