Bidirectional Modulation on Electroporation Induced by Membrane Tension Under the Electric Field

Electroporation ablation is a minimally invasive nonthermal ablation technology that is applied to tumor ablation therapy. Given the varied morphologies of tumor cells, when an electric field is applied to the cell membrane surface, the direction of the electric field produces various angles with normal to the tangential plane of the cell membrane. In this study, we investigated the impact of cell morphology on membrane electroporation characteristics by adjusting the angle of the electric field relative to the cell membrane by using molecular dynamics simulations. The results show that the bidirectional modulation of cell membrane surface tension induced by Coulomb force can be triggered, allowing the electroporation effect to be regulated, by varying the angle between the electric field direction and the normal to the membrane. Electric field angles below 45° decreased phospholipid membrane surface tension, facilitating pore formation; angles above 45° enhanced the surface tension, elevating the energy barrier for pore opening and thus inhibiting pore formation. Furthermore, during the initial stage of membrane pore formation, water molecules penetrated the lipids, which aligned with the electric field and affected the pore tilt. The bidirectional modulation of the electric field in electroporation demonstrated that reversing the angle of the electric field is a potentially effective electroporation ablation protocol for improving the effectiveness of clinical cancer treatments.