Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 110, Issue 3, Pages 842-847Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1217279110
Keywords
mechanotransduction; traction force microscopy
Categories
Funding
- National Science Foundation
- German Cancer Aid
- Sonderforschungsbereich [829 A1, Z2]
- National Science Foundation [DMR-0806511, DMR-1004789, DBI-0619674]
- National Institutes of Health [AR060295]
- Connecticut Department of Public Health [12-SCB-YALE-01]
- Yale University's Raymond and Beverly Sackler Institute for Biological, Physical, and Engineering Sciences
- Division Of Materials Research
- Direct For Mathematical & Physical Scien [1004789] Funding Source: National Science Foundation
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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 twoadhesion 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.
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