Membrane electroporation: chemical thermodynamics and flux kinetics revisited and refined

The chemical thermodynamic concept for membrane electroporation is critically revisited. The hysteresis in the electric field dependence of the rapid in-field electroporation events (on the in-field hysteresis branch) and the slower post-field pore resealing process (zero-field hysteresis branch) is a typical ensemble property involving rapid single-pore opening–closing events that are temporally and spatially distributed. In the case of spherical membrane shells in homogeneous external fields, the acting local field is dependent on the polar–angular position. Hence, the experimental state distribution constant and the ensemble rate coefficients are statistical position averages; they are cosine square averages of the polar angle. Advanced flux analysis uses the concept of time-dependent flux coefficients reflecting the kinetics of the rate-limiting structural processes of electroporation and membrane resealing. The explicit integral flux equations rationalize the sigmoid onset of the in-field kinetics and quantify the post-field-stretched exponentials as exponentials of exponentials. Finally, the new analytical proposal for the evaluation of the electric field strength dependence of global cell electroporation data starts with the low-field range and continues with iterative parameter optimisation over the entire field strength range.