Effects of heterogeneous membranes and electrolytes on electropore formation

Abstract

Atomistic simulations such as molecular dynamics (MD) simulations have revealed much about the fundamental biophysics of electroporation in homogeneous phospholipid bilayers; however, the structures and behaviors of live cellular membranes differ considerably from idealized zwitterionic lipid bilayers. Biological membranes contain both neutral and charged lipid types and interact with a large number of bulk and interfacial electrolytes that form complexes with individual lipids, thereby modulating their local surface tensions and creating domains and rafts regions. Even without considering the effects of transmembrane proteins, some of which are voltage-gated and are likely to perturb electropore formation and annihilation, the differences between electroporation in heterogeneous membranes, especially those containing salts, and homogeneous membranes described in the last section, are significant. This section will focus on how local perturbations to membranes such as the inclusion of anionic lipids, divalent cations such as calcium, oxidized lipids, and other additions can significantly change the behaviors of membrane electropermeabilization. Similarly, additional metrics such as calcium binding isotherms will be presented to assess the validity of these simulations and how well they relate to experiments. Finally, some additional studies will be discussed to deduce whether heterogeneous systems (more representative of live cellular membranes) form electropores with an exponential inverse dependence on applied voltage and electric field, as is observed for homogeneous systems.