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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Klingberg, F; Chow, ML; Koehler, A; Boo, S; Buscemi, L; Quinn, TM; Costell, M; Alman, BA; Genot, E; Hinz, B

Published Date

  • October 27, 2014

Published In

Volume / Issue

  • 207 / 2

Start / End Page

  • 283 - 297

PubMed ID

  • 25332161

Pubmed Central ID

  • 25332161

Electronic International Standard Serial Number (EISSN)

  • 1540-8140

Digital Object Identifier (DOI)

  • 10.1083/jcb.201402006

Language

  • eng

Conference Location

  • United States