Physical modelling of electroporation in close cell-to-cell proximity environments

Abstract

Many applications of electroporation, especially those utilizing electrofusion and in-vivo electroporation, involve cell environments that include close cell-to-cell proximity and a wide range of target cell size. It is important to understand how this kind of environment may alter optimum electroporation electrical parameters for any given application. A physical, electrically equivalent model of biological cell electroporation, based on aqueous solution filled thin latex rubber membrane spheroids, was used to investigate membrane permeabilization behaviour where there is both close cell-to-cell proximity and different cell radii. Cell model arrangements were pulsed using either a 50 µs or 10 µs, 1/e decay time constant dc capacitive discharge electric field, with peak amplitudes of 160-500 kV m⁻¹. Results indicate that, compared to cells in isolation, electroporation initiates at substantially decreased applied electric field magnitudes in regions of close cell-to-cell proximity where the external media conductivity is lower than the cell interior conductivity, and the membrane is maximally polarized. Additionally, the use of shorter time constant, higher peak magnitude pulse parameters should reduce the relative difference in threshold membrane permeabilization in regions of close cell-to-cell proximity for cells of different size so that the degree of electroporation is more uniform for variable size and shape target cell populations.