Time domain dielectric spectroscopy of biological cells after pulsed electric field exposure

Dielectric characteristics determine the initial response of a biological cell to pulsed electric field exposure. Conversely, pulsed electric field-induced membrane poration and electric field-triggered biological changes will affect these parameters. Accordingly, the time-resolved measurement of cellular dielectric properties allows us to assess conformational and functional changes of cells after exposure in real time, and in turn, evaluate and compare the efficacy of chosen pulse parameters. Moreover, cell specific differences might eventually permit us to design exposure conditions to preferentially target cells, such as cancer. To this end, we have investigated the dielectric properties of Jurkat cells, a malignant human T-cell line, before and after application of microsecond and nanosecond pulsed electric fields by means of time domain dielectric spectroscopy. We modeled electrode polarization by a constant-phase-angle element in series with the cell suspension and identified the dielectric spectrum of each element successfully. Further analysis, based on the combination of a Maxwell-Wagner mixture model and a singleshell cell model, shows increases in the plasma membrane conductivity, indicating that membrane poration has occurred. The induced changes were more significant for the nanosecond exposure, suggesting different membrane charging and pore-forming mechanisms. Using a double-shell model, we could also obtain the nuclear envelope conductivity. Significant changes in conductivity after nanosecond pulsed electric field exposure, indicate that ultrashort pulses had also affected intracellular structures, while microsecond pulses had no significant effect on these parameters.