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Rapid signal transduction in living cells is a unique feature of mechanotransduction
Yingxiao Wang, and
Departments of *Mechanical Science and Engineering and Bioengineering, University of Illinois at Urbana–Champaign, Urbana, IL 61801
Edited by Thomas P. Stossel, Harvard Medical School, Boston, MA, and approved March 12, 2008
Received for publication December 12, 2007.
It is widely postulated that mechanotransduction is initiatedat the local force–membrane interface by inducing localconformational changes of proteins, similar to soluble ligand-inducedsignal transduction. However, all published reports are limitedin time scale to address this fundamental issue. Using a FRET-basedcytosolic Src reporter in a living cell, we quantified changesof Src activities as a local stress via activated integrinswas applied. The stress induced rapid (<0.3 s) activationof Src at remote cytoplasmic sites, which depends on the cytoskeletalprestress. In contrast, there was no Src activation within 12s of soluble epidermal growth factor (EGF) stimulation. A 1.8-Pastress over a focal adhesion activated Src to the same extentas 0.4 ng/ml EGF at long times (minutes), and the energy levelsfor mechanical stimulation and chemical stimulation were comparable.The effect of both stress and EGF was less than additive. Nanometer-scalecytoskeletal deformation analyses revealed that the strong activationsites of Src by stress colocalized with large deformation sitesof microtubules, suggesting that microtubules are essentialstructures for transmitting stresses to activate cytoplasmicproteins. These results demonstrate that rapid signal transductionvia the prestressed cytoskeleton is a unique feature of mechanotransduction.