Format

Send to

Choose Destination
J Cell Biol. 2014 Oct 27;207(2):283-97. doi: 10.1083/jcb.201402006. Epub 2014 Oct 20.

Prestress in the extracellular matrix sensitizes latent TGF-β1 for activation.

Author information

1
Laboratory of Tissue Repair and Regeneration, Matrix Dynamics Group, Faculty of Dentistry, University of Toronto, Toronto, Ontario M5S 3E2, Canada.
2
Department of Fundamental Neurosciences, University of Lausanne, CH-1015 Lausanne, Switzerland.
3
Soft Tissue Biophysics Laboratory, Department of Chemical Engineering, McGill University, Montreal, Quebec H3A 2B2, Canada.
4
Laboratory of Extracellular Matrix Proteins, Department of Biochemistry and Molecular Biology, Faculty of Biology, University of València, 46100 València, Spain.
5
Program in Developmental and Stem Cell Biology, Hospital for Sick Children, University of Toronto, Toronto, Ontario M5G 1X8, Canada.
6
Centre Cardiothoracique de Bordeaux, U1045, Université de Bordeaux, F-33000 Bordeaux, France.
7
Laboratory of Tissue Repair and Regeneration, Matrix Dynamics Group, Faculty of Dentistry, University of Toronto, Toronto, Ontario M5S 3E2, Canada boris.hinz@utoronto.ca.

Abstract

Integrin-mediated force application induces a conformational change in latent TGF-β1 that leads to the release of the active form of the growth factor from the extracellular matrix (ECM). Mechanical activation of TGF-β1 is currently understood as an acute process that depends on the contractile force of cells. However, we show that ECM remodeling, preceding the activation step, mechanically primes latent TGF-β1 akin to loading a mechanical spring. Cell-based assays and unique strain devices were used to produce a cell-derived ECM of controlled organization and prestrain. Mechanically conditioned ECM served as a substrate to measure the efficacy of TGF-β1 activation after cell contraction or direct force application using magnetic microbeads. The release of active TGF-β1 was always higher from prestrained ECM as compared with unorganized and/or relaxed ECM. The finding that ECM prestrain regulates the bioavailability of TGF-β1 is important to understand the context of diseases that involve excessive ECM remodeling, such as fibrosis or cancer.

Comment in

PMID:
25332161
PMCID:
PMC4210443
DOI:
10.1083/jcb.201402006
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center