Lipid pores: Molecular and continuum models

Abstract

Exposure of cells to pulsed electric fields has become a routine technique to increase the permeability of cell membranes, allowing enhanced transmembrane transport of drugs, genetic material, and other molecules. The full details of the molecular mechanisms, which lead to the increased membrane permeability, are not yet entirely clear. However, extensive theoretical and experimental studies on model lipid systems demonstrated that formation of aqueous pores in the lipid bilayer presents one of the structural alterations of the cell membrane, which are induced under the influence of the electric field. The first theoretical arguments supporting the pore formation hypothesis were based on simple models, which treated the pores in terms of continuum (mesoscopic) theories. Later on, insights from molecular dynamics (MD) simulations substantiated some of the predictions arising from continuum models and, in addition, provided a comprehensive molecular picture of the pore formation process. The present chapter gives a brief overview of MD simulations and continuum modeling of lipid pores, with specific aim to highlight their connections, agreements, and disagreements. Establishing connections between these two modeling approaches is highly beneficial in order to enhance the understanding of electroporation. On one hand, MD simulations provide a direct method for seeking the molecular mechanisms of pore formation, and they compensate for the lack of microscopic techniques to visualize lipid pores. On the other hand, continuum models, which are computationally much less demanding, can often be more easily applied to theoretically analyze complex experimental systems. MD simulations could therefore be used to validate and improve continuum models, whereas continuum models could serve as a bridge between MD simulations and experiments.