Structural Thermodynamics of Membrane Electroporation: Voltage-Driven Interdigitation Induces Electro-Topological Disparity

This is the authors' abstract. We don't add key points for this paper.

-profiles of membrane potential and water-dipole orientation largely mirror bulk behavior, showing that global averaging masks the pore-core electrostatic response and necessitating characteristic-radius-resolved local sampling. Crucially, high applied potentials induce an electro-topological disparity: voltage-driven leaflet interpenetration structurally outpaces aqueous pore dilation. Radius-resolved electrostatic matrices, phenotype clustering, and state-progression analyses show that interdigitation-defined local domains concentrate core water ordering and potential amplification. Rather than a simple nanoscale hole, this extensive electro-deformation generates an expanded "lipid scar" characterized by substantial tail entanglement, sharp lateral sterol gradients, and localized electrostatic enrichment. This amplified structural prestrain creates a thermodynamically vulnerable domain, potentially lowering the activation energy for consecutive poration, clarifying the molecular origins of electrosensitization in pulsed electric field therapies.