Model Assessment of Cell Membrane Breakdown in Clusters and Tissues Under High-Intensity Electric Pulsing

This paper presents a simulation study of cell membrane electroporation in clusters by high-intensity voltage pulses. The focus is on assessing effects associated with: 1) the variability in shape and randomness of the cells within clusters; 2) the density of clusters; 3) the effects in heterogeneous tissues; 4) the role of pulse width on fractional electroporation for given electrical characteristics; and 5) conductivity and cell shape influences on the electric strength versus pulse duration behavior. Quantitative results are obtained based on two-dimensional, time-dependent, random Voronoi network analyses. The calculations predict that it is harder to electroporate cells in a cluster due to the random orientation of cell boundaries with regard to the applied field. Also, with increasing cellular distortions and shape irregularity, the poration is predicted to require higher voltage amplitudes or longer pulse durations to cause the same effects. Intracellular conductivity was shown to be a primary parameter influencing cell membrane poration, with membrane permittivity having a secondary effect. This has implications for tissue selectivity, especially for ultrashort duration pulsing. Finally, strength-duration (S-D) curves have been obtained, and shown to depend on the relative disorder and randomness within clusters.