Inhibiting Effect of Inner Potential on Electroporation of Phospholipid Membranes Induced by Ionic Electrophoresis

Understanding electroporation at the molecular level is essential for advancing its biomedical applications, including drug delivery and tumor ablation. Among various influencing factors, the ionic environment, particularly ion concentration and type, plays a crucial role in modulating membrane behavior. In this study, we performed systematic molecular dynamics simulations to investigate how different ions affect the electroporation of phospholipid membranes. While moderate ion concentrations were found to accelerate pore formation by enhancing ion–membrane interactions, our results reveal that excessively high ion concentrations inhibit electroporation. Further analysis shows that this inhibition is primarily due to the formation of an inner potential, induced by the electrophoretic movement of ions under an applied field. This inner potential effectively weakens the transmembrane electric field, delaying or even preventing pore formation. Additionally, we demonstrate a strong correlation between ion charge concentration and electroporation time, regardless of ion species. These findings uncover a concentration-dependent shift in electroporation mechanisms and highlight the critical role of inner potential in regulating membrane permeability. This work provides valuable theoretical insights for the precise control and optimization of electroporation-based therapies.