Figure 2. Integrin-mediated TGFβ1 activation by cell contraction. Structural and force spectroscopy data suggest that the transforming growth factor-β1 (TGFβ1) and latent TGFβ1 binding protein-1 (LTBP-1) binding domains of the latency-associated peptide (LAP) act as a sensor in a mechanical model of integrin-mediated TGFβ1 activation. Mechanical stretch, applied through cell integrins will open the latent TGFβ1 complex to release TGFβ1. Flexible domains in the LAP that are prone to unfolding lie within a domain that has been coined “straitjacket.”¹⁷⁹ In the context of a poorly organized and compliant matrix and when cells develop only low contractile activity, the lack of sufficient mechanical tension will prevent the integrin-mediated conformational changes that are required to activate TGFβ1 from the latent complex. Conversely, on a stiff matrix the transmission of contractile forces via integrins to the LAP will favor unfolding of the straitjacket region, resulting in TGFβ1 release. Reproduced with permission.¹⁸⁴