Cited by 243Cellular Mechanics and InteractionsCell Adhesion Molecules ResearchSkin and Cellular Biology Research

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

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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·2013·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.1217279110PMC PMC3549115

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Abstract

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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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)
ORCID: Banerjee, Shiladitya
Niessen, Carien M.
Marchetti, M. Cristina
Dufresne, Eric R.
Horsley, Valerie
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
DOI: 10.1073/pnas.1217279110
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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Cadherin-based intercellular adhesions organize epithelial cell–matrix traction forces

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