Permeabilizing Phospholipid Bilayers with Non-normal Electric Fields

Since 2003, molecular dynamics simulations of lipid bilayers have provided valuable insights into the mechanisms underlying electropermeabilization (electroporation)-an electric field-induced increase in the permeability of biological membranes. The convention in these studies has been to apply the electric field normal to the plane of the membrane. In a typical electroporation application, however, where the electric field is reasonably uniform and unidirectional, the field is perpendicular to the membrane only at a few locations-for spherical cells only at the poles of the cells along the axis defined by the direction of the electric field. Everywhere else on the cell surface the field is applied at an angle that is oblique to the plane of the membrane. On a microscopic level, the invaginations and protrusions that characterize a living cell membrane also present many angles to the applied electric field. Here we report the results of molecular dynamics simulations of lipid electropore formation when the electric field is not normal to the membrane surface, which show that the tangential component of the field has a small but non-zero effect.