Effect of Monovalent Ion Concentration in Molecular Simulation of Electroporation

Abstract

Monovalent ion concentration gradients, regulated by ion pumps and leak channels, are critical components of many cellular functions. This dynamic balance is disturbed by the electroporative permeabilization of the cell membrane, which bypasses the normal membrane barriers to transmembrane ion flux. A better understanding of ion transport during and after electroporation will enable more efficient and more effective utilization of this method in biomedicine and biotechnology.Molecular dynamics (MD) simulations provide a view of the behavior of ions and biomolecular structures at the molecular level. Previous MD studies have demonstrated some of the effects of monovalent ions on phospholipid bilayers, including decreased area per lipid, higher ordering in head group vertical orientations, and decreased lateral lipid mobility [1-4]. MD simulations of porated membranes have also shown that the binding of monovalent cations to phospholipids can increase pore line tension, which leads to a decrease in pore lifetime [5]. In this work we employ MD simulations to systematically study the effects of varying the concentration of Na+, K+, and Cl− in POPC lipid bilayer systems during different stages of electropore formation.1.Gurtovenko, A.A. and I. Vattulainen, J Phys Chem B, 2008. 112(7): p. 1953-62.2.Vacha, R., et al., Journal of Physical Chemistry A, 2009. 113(26): p. 7235-7243.3.Vacha, R., et al., J Phys Chem B, 2010. 114(29): p. 9504-9.4.Jurkiewicz, P., et al., Biochim Biophys Acta, 2012. 1818(3): p. 609-16.5.Leontiadou, H., A.E. Mark, and S.J. Marrink, Biophys J, 2007. 92(12): p. 4209-15.