Numerical study of the electroporation pulse shape effect on molecular uptake of biological cells

Abstract

Background. In order to reduce the side-effects of chemotherapy, combined chemotherapy-electroporation (electrochemotherapy) has been suggested. Electroporation, application of appropriate electric pulses to biological cells, can significantly enhance molecular uptake of cells due to formation of transient pores in the cell membrane. It was experimentally demonstrated that the efficiency of electroporation is under the control of electric pulse parameters. However, the theoretical basis for these experimental results is not fully explained. In order to predict the outcome of experiments and optimize the efficiency of electroporation before each treatment, we developed a model to investigate the effect of pulse shape on efficiency of electroporation. Results. Our model is based on a developed chemical-kinetics scheme and trapezium barrier model, while selfconsistency was taken into account. This model is further supplemented with a molecular transport model to acquire the molecular uptake of cells. The investigated pulse shapes in this study were unipolar rectangular pulses with different rise and fall times, triangular, sinusoidal and bipolar rectangular pulses and also sinusoidal modulated unipolar pulses with different percentages of modulation. The obtained results from our modelling and simulations are in good agreement with previously published experimental results. Conclusions. We therefore conclude that this model can be used to predict the effects of arbitrarily shaped electroporation pulses on cell membrane conductivity and molecular transport across the cell membrane.