Editors' ChoiceMechanotransduction

Faster Than a Speeding Molecule

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Science Signaling  13 May 2008:
Vol. 1, Issue 19, pp. ec175
DOI: 10.1126/stke.119ec175

Mechanotransduction is the process by which external physical forces induce intracellular responses. Na et al. examined the velocity with which the tyrosine kinase Src could be activated by mechanical stress as compared with epidermal growth factor (EGF) signaling. The authors measured Src activation with a reporter that consisted of a yellow fluorescent protein (YFP) and cyan fluorescent protein (CFP) tethered to one another by a short (12-amino acid) Src substrate peptide. When the peptide is not bound by Src, the fluorescent tags are close enough to interact, producing a high fluorescence resonance energy transfer (FRET) ratio, but upon binding by Src, the tags are displaced, producing a low FRET ratio. The authors added magnetic beads coated with the tripeptide Arg-Gly-Asp to cultured fibroblasts to induce the cells to form focal adhesions with the beads and then used a magnetic field to deliver mechanical stress to the cells. Focal adhesions were required for mechanical stress-induced Src activation, because cells that were not induced to form focal adhesions exhibited no Src activation in response to a magnetic field. By using fluorescently labeled tubulin and a microscopic method for mapping microtubule deformations, the authors found that Src activation colocalized with the regions of greatest microtubule deflections. Mechanical stimulation of Src activity was much faster than stimulation through the EGF pathway. Whereas application of purified EGF resulted in Src activation in 12 seconds, mechanical stress activated Src in as little as 0.3 seconds, much faster than could be accomplished by a pathway that relied on either passive diffusion or active transport of molecules to relay the signal inside the cell. Only cells plated on stiff (as opposed to soft) substrates exhibited Src activation by mechanotransduction, so the phenomenon also required that the cytoskeleton be prestressed; much like a spider’s web, the cytoskeletal network could transmit mechanical stress signals only when tensioned. The authors proposed that the cytoskeleton conveyed the mechanical force into the cytoplasm by vibrating or stretching. Mechanotransduction, then, may enable nearly simultaneous, though nonspecific, activation of molecules near the plasma membrane and deep inside the cytoplasm.

S. Na, O. Collin, F. Chowdhury, B. Tay, M. Ouyang, Y. Wang, N. Wang, Rapid signal transduction in living cells is a unique feature of mechanotransduction. Proc. Natl. Acad. Sci. U.S.A. 105, 6626-6631 (2008). [Abstract] [Full Text]