Cadherin-based intercellular adhesions organize epithelial cell–matrix traction forces

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 110; no. 3; pp. 842 - 847
• Main Authors: Mertz, Aaron F., Che, Yonglu, Banerjee, Shiladitya, Goldstein, Jill M., Rosowski, Kathryn A., Revilla, Stephen F., Niessen, Carien M., Marchetti, M. Cristina, Dufresne, Eric R., Horsley, Valerie
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 15-01-2013; National Acad Sciences
• Subjects: Actins; Animals; Biological Sciences; Biophysical Phenomena; Cadherins; Cadherins - antagonists & inhibitors; Cadherins - deficiency; Cadherins - genetics; Cadherins - physiology; Calcium; Calcium - pharmacology; Cell adhesion; Cell adhesion & migration; Cell Adhesion - drug effects; Cell Adhesion - physiology; Cells, Cultured; Cellular biology; Culture Media - analysis; Endothelial cells; Epithelial cells; Flux density; Focal adhesions; Gene expression; Gene Knockdown Techniques; Gene Knockout Techniques; Homeostasis; Intercellular Junctions - drug effects; Intercellular Junctions - physiology; Keratinocytes; Keratinocytes - drug effects; Keratinocytes - physiology; Mechanotransduction, Cellular - drug effects; Mechanotransduction, Cellular - physiology; Mice; Models, Biological; Physical Sciences; RNA, Small Interfering - genetics; Rodents; Signal transduction; Stem cells; Tissues
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1217279110

Cell–cell and cell–matrix adhesions play essential roles in the function of tissues. There is growing evidence for the importance of cross talk between these two adhesion types, yet little is known about the impact of these interactions on the mechanical coupling of cells to the extracellular matrix (ECM). Here, we combine experiment and theory to reveal how intercellular adhesions modulate forces transmitted to the ECM. In the absence of cadherin-based adhesions, primary mouse keratinocytes within a colony appear to act independently, with significant traction forces extending throughout the colony. In contrast, with strong cadherin-based adhesions, keratinocytes in a cohesive colony localize traction forces to the colony periphery. Through genetic or antibody-mediated loss of cadherin expression or function, we show that cadherin-based adhesions are essential for this mechanical cooperativity. A minimal physical model in which cell–cell adhesions modulate the physical cohesion between contractile cells is sufficient to recreate the spatial rearrangement of traction forces observed experimentally with varying strength of cadherin-based adhesions. This work defines the importance of cadherin-based cell–cell adhesions in coordinating mechanical activity of epithelial cells and has implications for the mechanical regulation of epithelial tissues during development, homeostasis, and disease.