Integrins as biomechanical sensors of the microenvironment
Abstract
Integrins, and integrin-mediated adhesions, have long been recognized to provide the main molecular link attaching cells to the extracellular matrix (ECM) and to serve as bidirectional hubs transmitting signals between cells and their environment. Recent evidence has shown that their combined biochemical and mechanical properties also allow integrins to sense, respond to and interact with ECM of differing properties with exquisite specificity. Here, we review this work first by providing an overview of how integrin function is regulated from both a biochemical and a mechanical perspective, affecting integrin cell-surface availability, binding properties, activation or clustering. Then, we address how this biomechanical regulation allows integrins to respond to different ECM physicochemical properties and signals, such as rigidity, composition and spatial distribution. Finally, we discuss the importance of this sensing for major cell functions by taking cell migration and cancer as examples.
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CAFs produce matrix-crosslinking enzymes and, together with force-mediated ECM remodelling, these contribute to increased stiffness of tumour tissue.
“CAFs also produce matrix-crosslinking enzymes and, together with force-mediated ECM remodelling (reviewed in detail85,86), these contribute to the increased stiffness of tumour tissue87–89.”
From A framework for advancing our understanding of cancer-associated fibroblasts (2020) · cites this paper as [85]
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Self-citation
- Authors
- Kechagia, J. Z., Ivaska, J., & Roca-Cusachs, P.
- Affiliations
- Åbo Akademi University (FI)
- Corresponding author
- Ivaska, Johanna
- Venue
- Nature Reviews Molecular Cell Biology
- Published
- 2019-06-10
- Volume
- 20
- Issue
- 8
- Pages
- 457-473
- ISSN
- 1471-0072 (ISSN-L)
- 1471-0080
- OpenAlex
- W2951737903
- Cited by
- 1,311
- References
- 8
- Citations by year
- 2026: 149 · 2025: 189 · 2024: 204 · 2023: 186 · 2022: 219 · 2021: 204 · 2020: 145 · 2019: 13 · 2015: 1
- FWCI
- 18.80
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nature Reviews Molecular Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- Dipòsit Digital de la Universitat de Barcelona (Universitat de Barcelona) (submittedVersion, public-domain)
- Topics
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Physical Sciences › Physics and Astronomy › Atomic and Molecular Physics, and Optics › Force Microscopy Techniques and Applications
- Keywords
- integrins, integrin-mediated adhesion, extracellular matrix, cell-matrix mechanics, biomechanical sensing, integrin activation, integrin clustering, cell migration, cancer, ECM composition, cell microenvironment
- MeSH terms
- Animals, Cell Adhesion, Cell Membrane, Cell Movement, Extracellular Matrix, Humans, Neoplasm Proteins, Neoplasms, Integrins, Tumor Microenvironment
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