Molecular Dynamics Study of Plasma Membrane Electroporation Under Bipolar Pulses

The action mechanism of bipolar pulse (BP) on biological plasma membranes─which boast complex compositions and asymmetric lipid distributions between the inner and outer leaflets─remains incompletely elucidated. In this study, coarse-grained molecular dynamics (MD) simulation techniques were used to conduct a systematic investigation of the mammalian average plasma membrane model, aiming to analyze the effects of BP and its application sequence on the electroporation process of the plasma membrane. During the experiments, two BP modes were used: depolarization-hyperpolarization bipolar pulses (D-H BP) and hyperpolarization-depolarization bipolar pulses (H-D BP). In both BP modes, we found that the plasma membrane exhibited two distinct electroporation states at the end of the pulse interval, which were defined as the Retaining state and the Resealing state. As the interval lengthens, the frequency of the Retaining state progressively declines, while that of the Resealing state steadily rises. Under H-D BP, the plasma membrane exhibits a higher frequency of the Retaining state and a notably larger perforation area compared to D-H BP. Analyzed within the Martini coarse-grained framework, our results primarily reveal a qualitative trend regarding the application sequence of BP. This trend suggests that the sequence may be a relevant factor for the electroporation (EP) process, potentially affecting pore expansion and localization, a finding that warrants further investigation.