Substrate-mediated mechanical interactions induce multicellular network formation*

Cells sense their surroundings by exerting mechanical forces on their viscoelastic substrate. We show, through agent-based simulations of cells modeled as motile, contractile force dipoles on elastic substrates, that mechanical interactions result in cell networks. These resemble networks of endothelial cells, a precursor to blood vessel formation. The morphology of the simulated networks is quantified by several metrics, including the percolation transition and a fractal dimension. Model networks are found to have a fractal dimension comparable to leaf and animal venation, and significantly lower than the control case of randomly moving adhesive agents. This shows that cells directed by substrate mediated elastic interactions can more efficiently form space-spanning structures. Next, we investigate the dynamics of cell-cell interactions by considering timescales from substrate viscoelasticity and force dipole generation. Additionally, we simulate a finite elastic medium, to examine the possible feedback between cell network formation and macroscopic gel contraction.