Tension reduction from inter-membrane counter-deformation accelerates nuclear electroporation

Pulsed electric field ablation is an emerging non-thermal modality for tumor treatment, in which electroporation of both the plasma membrane and the nuclear envelope plays a critical role in inducing irreversible cellular damage. To elucidate the different effects of nanosecond pulsed electric fields (nsPEFs) on these membranes, we compared the electroporation responses of the single and double membranes under the same field strength employing molecular dynamics (MD) simulations. Our results demonstrate that the double membrane underwent faster electroporation, attributed to inter-membrane counter-deformation under Coulomb force, which modulated the local electric field direction and reduced membrane tension. Compared to the single membrane, the double membrane may be more susceptible to damage induced by nsPEFs. This finding may provide a molecular-scale theoretical reference for understanding the electroporation mechanism of the nuclear envelope relative to the plasma membrane under nsPEFs.