Dependence of Tensional Homeostasis on Cell Type and on Cell-Cell Interactions

The ability to maintain a homeostatic level of cell tension is essential for many physiological processes. Our group has recently reported that multicellularity is required for tensional homeostasis in endothelial cells. However, other studies have shown that isolated fibroblasts also maintain constant tension over short time scales without the need of cell-cell contacts. Therefore, in this study, our aim was to determine how different cell types regulate tension as isolated cells or in small clustered groupings and to investigate the role of cell-cell adhesion molecules, such as E-cadherin, in this system.

Micropattern traction force microscopy was used to determine how bovine aortic endothelial cells, bovine vascular smooth muscle cells, mouse embryonic fibroblasts, and human gastric adenocarcinoma cells, with or without cell-cell interactions due to E-cadherin, maintain tensional homeostasis over time. Tension temporal fluctuations in single cells and cell clusters were evaluated.

We found that only endothelial cells require clustering for tensional homeostasis. The same was not verified in fibroblasts or vascular smooth muscle cells. Of relevance, in adenocarcinoma cells, we verified that tensional homeostasis was dependent on the competence of the adhesion molecule E-cadherin at both the single cells and multicellular levels.

These findings indicate that cell-cell contacts may be critical for tensional homeostasis and, potentially, for barrier function of the endothelium. Furthermore, the cell-cell adhesion molecule E-cadherin is an important regulator of tensional homeostasis, even in the absence of cadherin engagement with neighboring cells, which demonstrates its relevance not only as a structural molecule but also as a signaling moiety.