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Mechanical stability of talin rod controls cell migration and substrate sensing

Rahikainen, R.; Von Essen, M.; Schaefer, M.; Qi, L.; Azizi, L.; Kelly, C.; Ihalainen, T. O.; Wehrle-Haller, B.; Bastmeyer, M.; Huang, C.; Hytönen, V. P.

Cells adhere to the surrounding tissue and probe its mechanical properties by forming cell-matrix adhesions. Talin is a critical adhesion protein and participates in the transmission of mechanical signals between extracellular matrix and cell cytoskeleton. Force induced unfolding of talin rod subdomains has been proposed to act as a cellular mechanosensor, but so far evidence linking their mechanical stability and cellular response has been lacking. Here, by utilizing computationally designed mutations, we demonstrate that stepwise destabilization of the talin rod R3 subdomain decreases cellular traction force generation, which affects talin and vinculin dynamics in cell-matrix adhesions and results in the formation of talin-rich but unstable adhesions. We observed a connection between talin stability and the rate of cell migration and also found that talin destabilization affects the usage of different integrin subtypes and sensing of extracellular matrix proteins. Experiments with truncated forms of talin confirm the mechanosensory role of the talin R3 subdomain and exclude the possibility that the observed effects are caused by the release of talin head-rod autoinhibition. ... mehr

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DOI: 10.5445/IR/1000071793
DOI: 10.1038/s41598-017-03335-2
Zitationen: 27
Web of Science
Zitationen: 26
Zitationen: 29
Cover der Publikation
Zugehörige Institution(en) am KIT Institut für Funktionelle Grenzflächen (IFG)
Zoologisches Institut (ZOO)
Publikationstyp Zeitschriftenaufsatz
Publikationsjahr 2017
Sprache Englisch
Identifikator ISSN: 2045-2322
KITopen-ID: 1000071793
HGF-Programm 47.02.06 (POF III, LK 01) Zellpopul.auf Biofunk.Oberflächen IFG
Erschienen in Scientific reports
Verlag Nature Research
Band 7
Seiten Art. Nr. 3571
Nachgewiesen in Scopus
Web of Science
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