Mechanotransduction in vivo by repeated talin stretch-relaxation events depends upon vinculin

Felix Margadant, Li Li Chew, Xian Hu, Hanry Yu, Neil Bate, Xian Zhang, Michael Sheetz

Research output: Contribution to journalArticle

124 Citations (Scopus)

Abstract

Mechanotransduction is a critical function for cells, in terms of cell viability, shaping of tissues, and cellular behavior. In vitro, cellular level forces can stretch adhesion proteins that link extracellular matrix to the actin cytoskeleton exposing hidden binding sites. However, there is no evidence that in vivo forces produce significant in vivo stretching to cause domain unfolding. We now report that the adhesion protein, talin, is repeatedly stretched by 100-350 nm in vivo by myosin contraction of actin filaments. Using a functional EGFP-N-Talin1-C-mCherry to measure the length of single talin molecules, we observed that the C-terminal mCherry was normally displaced in the direction of actin flow by 90 to >250 nm from N-EGFP but only by 50-60 nm (talin's length in vitro) after myosin inhibition. Individual talin molecules transiently stretched and relaxed. Peripheral, multimolecular adhesions had green outside and red proximal edges. They also exhibited transient, myosin-dependent stretching of 50-350 nm for 6-16 s; however, expression of the talin-binding head of vinculin increased stretching to about 400 nm and suppressed dynamics. We suggest that rearward moving actin filaments bind, stretch, and release talin in multiple, stochastic stick-slip cycles and that multiple vinculin binding and release cycles integrate pulling on matrices into biochemical signals.

Original languageEnglish (US)
Article numbere1001223
JournalPLoS Biology
Volume9
Issue number12
DOIs
StatePublished - Dec 1 2011
Externally publishedYes

Fingerprint

talin
Talin
Vinculin
Actins
Myosins
myosin
microfilaments
Actin Cytoskeleton
Stretching
adhesion
Adhesion
Stick-slip
Molecules
Extracellular Matrix Proteins
extracellular matrix
cell viability
actin
mechanotransduction
binding sites
Cell Survival

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Mechanotransduction in vivo by repeated talin stretch-relaxation events depends upon vinculin. / Margadant, Felix; Chew, Li Li; Hu, Xian; Yu, Hanry; Bate, Neil; Zhang, Xian; Sheetz, Michael.

In: PLoS Biology, Vol. 9, No. 12, e1001223, 01.12.2011.

Research output: Contribution to journalArticle

Margadant, Felix ; Chew, Li Li ; Hu, Xian ; Yu, Hanry ; Bate, Neil ; Zhang, Xian ; Sheetz, Michael. / Mechanotransduction in vivo by repeated talin stretch-relaxation events depends upon vinculin. In: PLoS Biology. 2011 ; Vol. 9, No. 12.
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