Giant pore formation in vesicles under msPEF-induced electroporation: role of charging time and waveform

Abstract

Giant unilamellar vesicle is the closest possible prototypical model for investigating membrane electrodeformation and electroporation in biological cells. In this paper, the effect of membrane charging time on vesicle electroporation, an unresolved issue, is exclusively investigated under milli-second pulsed-electric-field (msPEF) of different waveforms, using numerical simulations. The existing analytical models uncover several fundamental features of cell or vesicle electroporation, but remain far from being realistic as electrode-formation effects were neglected. Our numerical approach, which implements the effect of electric stretching on membrane tension and precise calculation of pore energy, successfully predicts the formation of giant pores of O({micro}m) size as observed in past experiments. The poration zone is found to extend up to certain angles from the poles, termed critical angles. Increase in charging time delays pore formation, decreases the pore density as well as trim downs the poration zone. Counterintuitively, this effect promotes significant pore growth. Thus, more pores evolve into giant pores resulting in higher fractional pore area. Moreover, there exists a cut-off charging time above which pore formation is completely inhibited. This phenomenon is particularly pronounced with bipolar pulses. Comparisons with the past experimental results reveal that electrodeformation-poration-induced membrane surface area variation and that induced by electroporation evolves in a similar fashion. Therefore, although the agreements are qualitative, the present electroporation model can be used as the simplest tool to predict the transient electrodeformation of a porated vesicle in the laboratory experiments.