A molecular insight into the electro-transfer of small molecules through electropores driven by electric fields.

The transport of chemical compounds across the plasma membrane into the cell is relevant for several biological and medical applications. One of the most efficient techniques to enhance this uptake is reversible electroporation. Nevertheless, the detailed molecular mechanism of transport of chemical species (dyes, drugs, genetic materials, …) following the application of electric pulses is not yet fully elucidated. In the past decade, molecular dynamics (MD) simulations have been conducted to model the effect of pulsed electric fields on membranes, describing several aspects of this phenomenon. Here, we first present a comprehensive review of the results obtained so far modeling the electroporation of lipid membranes, then we extend these findings to study the electrotransfer across lipid bilayers subject to microsecond pulsed electric fields of Tat11, a small hydrophilic charged peptide, and of siRNA. We use in particular a MD simulation protocol that allows to characterize the transport of charged species through stable pores. Unexpectedly, our results show that for an electroporated bilayer subject to transmembrane voltages in the order of 500mV, i.e. consistent with experimental conditions, both Tat11 and siRNA can translocate through nanoelectropores within tens of ns. We discuss these results in comparison to experiments in order to rationalize the mechanism of drug uptake by cells. This article is part of a Special Issue entitled: Biosimulations edited by Ilpo Vattulainen and Tomasz Róg.