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Cadherin-based intercellular adhesions organize epithelial cell–matrix traction forces
Open accessAbstract
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.
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“Moreover, loss of E-cadherin interfered with coordinated transfer of force across multiple cells to cell–matrix adhesion sites at edges of multicellular colonies (Fig. 5e, f)24.”
From E-cadherin integrates mechanotransduction and EGFR signaling to control junctional tissue polarization and tight junction positioning (2017) · cites this paper as [24]
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Cites
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Metadata
- Authors
- Mertz, A. F., Che, Y., Banerjee, S., Goldstein, J. M., Rosowski, K. A., Revilla, S. F., Niessen, C. M., Marchetti, M. C., Dufresne, E. R., & Horsley, V.
- Affiliations
- Departments of aPhysics,
- Department of Physics, and
- Molecular, Cellular, and Developmental Biology,
- Maryville College (US)
- University of Cologne (DE)
- Syracuse University (US)
- Yale University (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2012-12-31
- Volume
- 110
- Issue
- 3
- Pages
- 842-847
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3549115
- OpenAlex
- W2162198931
- Cited by
- 243
- References
- 72
- Citations by year
- 2026: 14 · 2025: 13 · 2024: 11 · 2023: 14 · 2022: 17 · 2021: 20 · 2020: 18 · 2019: 17 · 2018: 20 · 2017: 21 · 2016: 26 · 2015: 25 · 2014: 18 · 2013: 9
- FWCI
- 7.87
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- arXiv (Cornell University) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- arXiv (Cornell University)
- Funders
- Yale University
- National Institute of General Medical Sciences (T32GM007223)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR060295, AR060295)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Skin and Cellular Biology Research
- Keywords
- cell-cell adhesion, cell-matrix adhesion, traction force, epithelial mechanics, keratinocytes, mechanical coupling, extracellular matrix, cell contractility, physical model, force localization, tissue mechanics
- MeSH terms
- Animals, Calcium, Cell Adhesion, Cells, Cultured, Culture Media, Intercellular Junctions, Models, Biological, Keratinocytes, Cadherins, RNA, Small Interfering, Mechanotransduction, Cellular, Mice, Biophysical Phenomena, Gene Knockdown Techniques, Gene Knockout Techniques
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