Substrate stiffness and mechanical stress due to intercellular cooperativity guides tissue structure

A key challenge in cell and tissue morphogenesis is to understand how a crucial balance between cell proliferation and apoptosis maintains an evolving tissue structure. These processes are mutually non-exclusive and require stiffness monitoring of the host substrate. Adhered cells actively mechanosense the tension in the extracellular matrix (ECM). They collectively alter self-organization and generate a host of tissue patterns. Using an in silico elastic fiber-network in two dimensions, we simulate cell-ECM composite structures and characterize features of the emerging tissue patterns during successive cell proliferation and apoptosis. Our data reveals that, in general, cell viability is a function of the cell-induced effective ECM stiffness supported by intercellular cooperativity. Translating this into a remodeling tissue, we find that average cell cycle duration in concert with the locally stressed regions of the ECM promote heterogeneous proliferation and apoptosis inducing finger-like protrusions along the tissue periphery - a feature normally observed during tumorigenesis. Further, we find that recovery of a scratch wound is delayed for cells harbored on a compliant or (and) in a highly collagen depleted ECM.