Spatial mechanistic modeling for prediction of 3D multicellular spheroids behavior upon exposure to high intensity pulsed electric fields

Abstract

The objective of this work was to investigate the growth specificities of cancer cells spheroids subjected to pulsed electric field. Multicellular HCT-116-GFP spheroids were exposed to different electric field intensities and the volume of multicellular spheroids was monitored by fluorescence and bright field microscopy. Thanks to an advanced mathematical model, based on differential equations and well-adapted estimation strategies, our modeling enables us to characterize the multicellular spheroids growth after permeabilizing pulsed electric field. In particular, we identify the percentage of cells which are destroyed and the percentage of cells which exhibit an altered growth pattern for different magnitudes of the electric field. We also quantify the growth resumption upon reversible and partially irreversible electroporation. Our preliminary results provide a first quantification of the impact of electroporation on multicellular spheroids growth, and suggest a booming growth of partially irreversible electric pulses, leading to an accelerated regrowth.