Mechanobiology of the cell-matrix interplay: Catching a glimpse of complexity via minimalistic models

Biological tissues present a grand challenge for mechanicians. Not only are their mechanical properties complex, they show a strong spatiotemporal heterogeneity due to ongoing and active remodeling of the living matter they are composed of: cells and extracellular matrix (ECM). The main sensors and effectors in this process are the cells, which direct tissue structure and mechanics by changing their own behavior and by producing and reorganizing the ECM. Vice versa, the ECM exhibits unique mechanical signatures associated with its fibrous polymer network that can modulate cell behavior. Grasping the full complexity of this reciprocal mechanical interaction between cells and the ECM is key for understanding physiological tissue function and maladaptation. An emerging approach is to explain the role of tissue biomechanics one component at a time and gradually (re)build tissue complexity. Here we highlight how this approach has been valuable in providing new insights in the relative and combined roles of cells and matrix, and in raising new questions into the origins of cellular and tissue responses. The answers may offer new approaches for mechanically driven tissue regeneration and biomaterial design.