Cell-cell interactions and the mechanics of cells and tissues observed in bioartificial tissue constructs

Mechanical interactions among cells in living tissues play central roles in several physiologic and pathologic phenomena. A large body of work from the mechanical study of cells in bioartificial tissue constructs sheds light on these interactions. This chapter summarizes models used to derive mechanical responses of cells from tissue constructs and then presents examples of three classes of biophysical observations that can be understood through simplified analysis of mechanical interactions between cells. The first observation is the effective mechanical behavior of cells: contractile fibroblast cells appear to modulate both their effective stiffness and that of the extracellular matrix in which they are embedded in a way that is regulated by their volume fraction within a tissue construct; these cells and their extracellular matrix have matched effective relaxed moduli of approximately 10-20 kPa when the volume fraction of cells within the tissue construct is that associated with the percolation threshold. Additionally, cells appear to proliferate or die off to reach this volume fraction. The second observation is the ensemble average mechanical properties of sub-cellular protein structures, when contractile fibroblasts exist at a volume fraction above the percolation threshold, the dynamic behaviors of their cytoskeletons are evident from the mechanics of the tissue as a whole. The third observation is the pathological effects of cell-cell interactions: tissue constructs containing both cardiomyocytes and proliferative cardiac fibroblasts serve as a model of fibrosis of the heart.