A unique feature of mechanotransduction is revealed

It is generally believed that similar to soluble ligand-induced signal transduction, mechanotransduction initiates at the local force-membrane interface (e.g., at focal adhesions) by inducing local conformational changes or unfolding of membrane-bound proteins, followed by a cascade of diffusion-based or translocation-based signaling in the cytoplasm. However, all published reports, including past studies with the reporter type of construct extended here, were limited in timescale to address this fundamental issue. Therefore, it has not been possible to compare early dynamics of mechanotransduction with that of soluble ligand-induced signal transduction. Using a FRET-based cytosolic Src reporter in a living cell, we quantified changes of Src activities as a local stress via activated integrins was applied. The stress induced rapid (<0.3 s) activation of Src at remote cytoplasmic sites, which depends on the cytoskeletal prestress. In contrast, there was no Src activation within 12 s of soluble epidermal growth factor stimulation. Nanometer scale cytoskeletal deformation analyses revealed that the strong activation sites of Src by stress colocalized with large deformation sites of microtubules.  Our findings suggest that microtubules are essential structures for transmitting stresses to activate cytoplasmic proteins by inducing conformational changes and that rapid signal transduction is a unique feature of mechanotransduction.