Mechanical stability of talin rod controls cell migration and substrate sensing

Abstract 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 r...

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Autores principales:	Rolle Rahikainen, Magdaléna von Essen, Markus Schaefer, Lei Qi, Latifeh Azizi, Conor Kelly, Teemu O. Ihalainen, Bernhard Wehrle-Haller, Martin Bastmeyer, Cai Huang, Vesa P. Hytönen
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/33e0adba084842f4828dc8e78f0a5053
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spelling	oai:doaj.org-article:33e0adba084842f4828dc8e78f0a50532021-12-02T12:30:54ZMechanical stability of talin rod controls cell migration and substrate sensing10.1038/s41598-017-03335-22045-2322https://doaj.org/article/33e0adba084842f4828dc8e78f0a50532017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03335-2https://doaj.org/toc/2045-2322Abstract 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. In conclusion, this study provides evidence into how the controlled talin rod domain unfolding acts as a key regulator of adhesion structure and function and consequently controls central cellular processes such as cell migration and substrate sensing.Rolle RahikainenMagdaléna von EssenMarkus SchaeferLei QiLatifeh AziziConor KellyTeemu O. IhalainenBernhard Wehrle-HallerMartin BastmeyerCai HuangVesa P. HytönenNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-15 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Rolle Rahikainen Magdaléna von Essen Markus Schaefer Lei Qi Latifeh Azizi Conor Kelly Teemu O. Ihalainen Bernhard Wehrle-Haller Martin Bastmeyer Cai Huang Vesa P. Hytönen Mechanical stability of talin rod controls cell migration and substrate sensing
description	Abstract 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. In conclusion, this study provides evidence into how the controlled talin rod domain unfolding acts as a key regulator of adhesion structure and function and consequently controls central cellular processes such as cell migration and substrate sensing.
format	article
author	Rolle Rahikainen Magdaléna von Essen Markus Schaefer Lei Qi Latifeh Azizi Conor Kelly Teemu O. Ihalainen Bernhard Wehrle-Haller Martin Bastmeyer Cai Huang Vesa P. Hytönen
author_facet	Rolle Rahikainen Magdaléna von Essen Markus Schaefer Lei Qi Latifeh Azizi Conor Kelly Teemu O. Ihalainen Bernhard Wehrle-Haller Martin Bastmeyer Cai Huang Vesa P. Hytönen
author_sort	Rolle Rahikainen
title	Mechanical stability of talin rod controls cell migration and substrate sensing
title_short	Mechanical stability of talin rod controls cell migration and substrate sensing
title_full	Mechanical stability of talin rod controls cell migration and substrate sensing
title_fullStr	Mechanical stability of talin rod controls cell migration and substrate sensing
title_full_unstemmed	Mechanical stability of talin rod controls cell migration and substrate sensing
title_sort	mechanical stability of talin rod controls cell migration and substrate sensing
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/33e0adba084842f4828dc8e78f0a5053
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_version_	1718394268684386304

Mechanical stability of talin rod controls cell migration and substrate sensing

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