A cross-scaled simulation on cell inactivation efficacy of pulsed electric fields by leveraging percolation theory

From the microscopic electroporation to the irregular distribution of cell populations, the inactivation efficacy of pulsed electric fields (PEFs) from in vitro experiments has lacked a unified physical model due to its cross-scale complexity. Inspired by a coarse-grained approach from the percolation theory, the inactivation process is simulated from a simple yet robust lattice model, where the spatiotemporal heterogeneity of the collective structure and the stochastic PEF strike are portrayed as random matrices, while also accounting for the rules of single-cell electroporation and subsequent death. Beyond successfully simulating the inactivation of monolayer adherent cells and suspended cells, which are in good agreement with in vitro results, our model reveals that (1) macroscopically three-staged inactivation pattern originates from the "accelerate-uniform-decelerate" transition of inactivation velocity, and (2) the inactivation patterns obey a universal scaling law under varied field strength, which is not satisfied under varied pulsed widths. The simulation not only sheds light on the PEF inactivation of the macroscopic cell collectives but also provides a simple and generalized numerical method for predicting PEF efficacy in experiments or engineering.