Skip to Content
Merck
  • Prestress in the extracellular matrix sensitizes latent TGF-β1 for activation.

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

The Journal of cell biology (2014-10-22)
Franco Klingberg, Melissa L Chow, Anne Koehler, Stellar Boo, Lara Buscemi, Thomas M Quinn, Mercedes Costell, Benjamin A Alman, Elisabeth Genot, Boris Hinz
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-Rabbit IgG (whole molecule)–FITC antibody produced in goat, affinity isolated antibody, buffered aqueous solution
Sigma-Aldrich
Anti-Integrin αVβ5 Antibody, clone P1F6, clone P1F6, Chemicon®, from mouse
Sigma-Aldrich
Anti-Integrin β3 Antibody, clone BB10, clone BB10, Chemicon®, from mouse
Sigma-Aldrich
Anti-Integrin αVβ3 Antibody, clone LM609, clone LM609, Chemicon®, from mouse
Sigma-Aldrich
Anti-Fibronectin antibody produced in rabbit, affinity isolated antibody, buffered aqueous solution
Sigma-Aldrich
Anti-Human IgG (Fc specific) antibody produced in rabbit, whole antiserum
Sigma-Aldrich
Anti-Integrin β1 Antibody, a.a. 82-87, clone JB1A (a.k.a. J10), ascites fluid, clone JB1A (J10), Chemicon®