Quantification of ion transport during cell electroporation theoretical and experimental analysis of transient and stable pores during cell electroporation

An increased permeability of a cell membrane during the application of high-voltage pulses results in increased transmembrane transport of molecules which otherwise can not enter the cell. This process known as electroporation or electropermeabilization is used in many biomedical applications including transfer of genes and electrochemotherapy of tumors. The induced transmembrane voltage leads presumably to the formation of structural changes (pores) in the cell membrane, however the molecular mechanisms of pore formation and stabilization are not fully explained. In this study we analyze together the transient conductivity changes during the pulses and increased membrane permeability for ions and molecules after the pulses. The conductivity of a cell suspension was measured during application of electrical pulses. By quantifying ion diffusion, efflux coefficients k due to the "transport" pores are obtained. We present a simple model which assumes a quadratic dependence of k(N) on E in the area where U > U(c) which very accurately describes experimental values. The results show that the fraction of the transport pores increases with higher electric field due to larger permeabilized area and due to higher energy, which is available for the formation of pores. kN increases also with the number of pulses, which suggest that each pulse contributes to formation of more stable transport pores.