Lipid electropore lifetime in molecular models

Abstract

Membrane electropermeabilization describes the electric field-mediated depolarization, and subsequent breakdown of cellular membranes, and is widely used in clinical and academic environments to deliver extracellular materials into the cell interior. Recently, these methods have contributed to the optimization of food sterilization and next-generation therapeutics that aim to enhance the susceptibility of tumor cells to traditional chemotherapies, signaling a significant shift in biomedical and medical modalities. However, the relationship between macroscale membrane electropermeabilization and the influx of individual materials through discrete electropores (often termed electroporation) is often unclear, at best. Because detection and characterization of discrete electropores in experiments containing cells or vesicles are difficult, if not impossible, this section will describe discrete electroporation models based on theoretical molecular dynamics simulations, with the intent of reconciling theoretical models with observations from macroscopic experiments. Access to massively parallel supercomputing resources have greatly enhanced the timescales and typical sample sizes modeled in simulations, and these trends are expected to grow as computing hardware and software become more integrated and affordable. Therefore, discussion will focus primarily on all-atom molecular models rather than larger, coarse-grained models that lack contributions from individual water molecules. Taken together, this section will broadly cover studies that aim to codify the discrete biophysical processes that mediate membrane electropermeabilization, in an effort to better understand its biological basis.