  We introduce a numerical framework that enables unprecedented direct
numerical studies of the electropermeabilization effects of a cell aggregate at
the meso-scale. Our simulations qualitatively replicate the shadowing effect
observed in experiments and reproduce the time evolution of the impedance of
the cell sample in agreement with the trends observed in experiments. This
approach sets the scene for performing homogenization studies for understanding
the effect of tissue environment on the efficiency of electropermeabilization.
We employ a forest of Octree grids along with a Voronoi mesh in a parallel
environment that exhibits excellent scalability. We exploit the electric
interactions between the cells through a nonlinear phenomenological model that
is generalized to account for the permeability of the cell membranes. We use
the Voronoi Interface Method (VIM) to accurately capture the sharp jump in the
electric potential on the cell boundaries. The case study simulation covers a
volume of $(1\ mm)^3$ with more than $27,000$ well-resolved cells with a
heterogeneous mix of morphologies that are randomly distributed throughout a
spheroid region.
