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.

Document Type

Article

Publication Date

6-15-2017

Notes/Citation Information

Published in Scientific Reports, v. 7, article no. 3571, p. 1-15.

© The Author(s) 2017

This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

Digital Object Identifier (DOI)

https://doi.org/10.1038/s41598-017-03335-2

Funding Information

Academy of Finland supported this research via grants 290506, 273192 and 136288 (for V.P.H). American Cancer Society supported the work by Research Scholar Grant RSG-13-184-01-CSM (for C.H). We thank University of Tampere for the financial support via TGPBB graduate school (for M. v. E). Finnish Cultural Foundation is acknowledged for the grant (for R.R). Swiss Foundation for Research on Myopathies (B. W.-H.), the Swiss National Science Foundation (31003A-130742) (B. W.-H.) and the Ligue Genevoise contre le Cancer are acknowledged (B.W.-H.).

Related Content

Supplementary information accompanies this paper at doi: 10.1038/s41598-017-03335-2

41598_2017_3335_MOESM1_ESM.pdf (1358 kB)
Supplementary Information

41598_2017_3335_MOESM2_ESM.avi (20470 kB)
Supplementary Movie S5

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