Electric-driven membrane poration. A rationale for water role in the kinetics of pore formation

Electroporation is a well-established technique used to stimulate cells, enhancing membrane permeability by inducing reversible membrane pores. In the absence of experimental observation of the dynamics of pore creation, molecular dynamics studies provide the molecular-level evidence that the electric field promotes pore formation. Although single steps in the pore formation process are well assessed, a kinetic model representing the mathematical description of the electroporation process, is lacking. In the present work we studied the basis of the pore formation process, providing a rationale for the definition of a first-order kinetic scheme. Here, authors propose a three-state kinetic model for the process based on the assessed mechanism of water defects intruding at the water/lipid interface, when applying electric field intensities at the edge of the linear regime. The methodology proposed is based on the use of two robust biophysical quantities analyzed for the water molecules intruding at the water/lipid interface: (i) number of hydrogen bonds; (ii) number of contacts. The final model, sustained by a robust statistical sampling, provides kinetic constants for the transitions from the intact bilayer state to the hydrophobic pore state.