Tensional homeostasis in multicellular clusters: effects of geometry and traction force dynamics

The ability of cells to maintain a constant level of their cytoskeletal tension in response to external and internal disturbances is referred to as tensional homeostasis. It is essential for the normal physiological function of cells and tissues, and for protection against disease progression, including atherosclerosis and cancer. It has been shown recently that some cell types, such as endothelial cells, can maintain tensional homeostasis only when they form multicellular clusters, whereas other cell types, such as fibroblasts, do not require clustering for tensional homeostasis. For example, measurements of cell-extracellular matrix traction forces have shown that temporal fluctuations of the traction field in clusters of endothelial cells become progressively attenuated with increasing number of cells in the cluster, whereas in fibroblasts cell clustering does not influence traction field variability. Mechanisms that are responsible for these observations are largely unknown. In this study, a theoretical analysis and mathematical modeling have been applied to analyze experimental data obtained previously from traction microscopy measurements in order to investigate possible physical mechanisms that influence temporal variability of the traction field in multicellular forms. The focus of the analysis is on the contribution of dynamics and distribution of focal adhesion traction forces in conjunction with geometrical shape and size of multicellular clusters. Results of the analysis revealed that cluster size, magnitude and temporal fluctuations of focal adhesion traction forces have a major influence on traction field variability, whereas the influence of cluster shape appears to be minor.