Quantifying Mechanical Interactions between Cells in Small Clusters

Tissue cells typically utilize their actomyosin contractile machinery to actively pull on their environment, which can be either the extracellular matrix or neighboring cells. The mechanical forces that a cell exerts and experiences have been shown to regulate fundamental cellular processes, including cell growth, proliferation, differentiation and migration. However, little is known about the spatial distribution of mechanical stress in tissues. In particular, the extent to which mechanical forces are communicated through cell-cell interactions across a tissue is not well understood.Here, we present a novel method, based on high resolution traction force microscopy, to measure mechanical stresses that are transmitted through cell-cell interfaces in small cellular clusters (∼10 cells). Cells are classified according to the number of neighboring cells. We find that this degree of cellular connectivity can determine many properties, including the amount of force transmitted through a particular cellular interface. In order to determine how force balance in the cell cluster is locally achieved, we compared forces transmitted through cells to forces exerted on the underlying substrate. A correlation analysis of these forces reveals the length scale over which forces can be transmitted through the cell cluster. Furthermore, by molecular perturbations, we are identifying proteins that may be essential for long range stress communication in the cluster. The ability to quantify force communication between cells will allow us to examine how cell-cell mechanical interactions contribute to overall tissue stress and vice versa. It will also allow us to investigate the role of mechanical stresses in establishing signaling gradients. This will further our understanding of the role of mechanical stress in processes that require fine coordination between cells, such as collective migration in morphogenesis and cancer.