The Single-Molecule Mechanics of the Latent TGF-beta 1 Complex

Background: TGF-beta 1 controls many pathophysiological processes including tissue homeostasis, fibrosis, and cancer progression. Together with its latency-associated peptide (LAP), TGF-beta 1 binds to the latent TGF-beta 1-binding protein-1 (LTBP-1), which is part of the extracellular matrix (ECM). Transmission of cell force via integrins is one major mechanism to activate latent TGF-beta 1 from ECM stores. Latent TGF-beta 1 mechanical activation is more efficient with higher cell forces and ECM stiffening. However, little is known about the molecular events involved in this mechanical activation mechanism.