Characterization of cell membrane permeability in vitro part ii: Computational model of electroporation-mediated membrane transport

Abstract

Electroporation is the process by which applied electric fields generate nanoscale defects in biological membranes to more efficiently deliver drugs and other small molecules into the cells. Due to the complexity of the process, computational models of cellular electroporation are difficult to validate against quantitative molecular uptake data. In part I of this two-part report, we describe a novel method for quantitatively determining cell membrane permeability and molecular membrane transport using fluorescence microscopy. Here, in part II, we use the data from part I to develop a two-stage ordinary differential equation model of cellular electroporation. We fit our model using experimental data from cells immersed in three buffer solutions and exposed to electric field strengths of 170 to 400 kV/m and pulse durations of 1 to 1000 μs. We report that a low-conductivity 4-(2-hydroxyethyl)-1 piperazineethanesulfonic acid buffer enables molecular transport into the cell to increase more rapidly than with phosphate-buffered saline or culture medium-based buffer. For multipulse schemes, our model suggests that the interpulse delay between two opposite polarity electric field pulses does not play an appreciable role in the resultant molecular uptake for delays up to 100 μs. Our model also predicts the per-pulse permeability enhancement decreases as a function of the pulse number. This is the first report of an ordinary differential equation model of electroporation to be validated with quantitative molecular uptake data and consider both membrane permeability and charging.