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PNAS 105 (18): 6626-6631

Copyright © 2008 by the National Academy of Sciences.


BIOLOGICAL SCIENCES / CELL BIOLOGY

Rapid signal transduction in living cells is a unique feature of mechanotransduction

Sungsoo Na*, Olivier Collin*, Farhan Chowdhury*, Bernard Tay*, Mingxing Ouyang{dagger}, Yingxiao Wang{dagger}, and Ning Wang*,{ddagger}

Departments of *Mechanical Science and Engineering and {dagger}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.

Abstract: It is widely postulated that mechanotransduction is initiated at the local force–membrane interface by inducing local conformational changes of proteins, similar to soluble ligand-induced signal transduction. However, all published reports are limited in time scale to address this fundamental issue. 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 (EGF) stimulation. A 1.8-Pa stress over a focal adhesion activated Src to the same extent as 0.4 ng/ml EGF at long times (minutes), and the energy levels for mechanical stimulation and chemical stimulation were comparable. The effect of both stress and EGF was less than additive. Nanometer-scale cytoskeletal deformation analyses revealed that the strong activation sites of Src by stress colocalized with large deformation sites of microtubules, suggesting that microtubules are essential structures for transmitting stresses to activate cytoplasmic proteins. These results demonstrate that rapid signal transduction via the prestressed cytoskeleton is a unique feature of mechanotransduction.

Key Words: cytoskeleton • growth factor • mechanical force • prestress • microtubule


Author contributions: S.N. and N.W. designed research; S.N., O.C., F.C., and M.O. performed research; S.N. and B.T. analyzed data; and S.N., Y.W., and N.W. wrote the paper.

The authors declare no conflict of interest.

This article is a PNAS Direct Submission.

This article contains supporting information online at www.pnas.org/cgi/content/full/0711704105/DCSupplemental.

{ddagger}To whom correspondence should be addressed. E-mail: nwangrw{at}uiuc.edu

© 2008 by The National Academy of Sciences of the USA


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