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The mechanical response of vinculin

Liu, Xuyao and Wang, Yinan and Yao, Mingxi and Baker, Karen and Klapholz, Benjamin and Brown, Nicholas H. and Goult, Benjamin T and Yan, Jie (2023) The mechanical response of vinculin. [Preprint] (doi:10.1101/2023.05.25.542235) (The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided) (KAR id:101416)

The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided.
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Vinculin is a mechanosensitive adapter protein that links the actin network to cell-extracellular matrix adhesions and cell-cell adhesions. It is perhaps the best characterized mechanoeffector, as it is recruited to sites of adhesion in response to force on the mechanotransducers talin and alpha-catenin. Here we examined the mechanical properties of vinculin to assess its potential role as a mechanotransducer. We find that at physiological loading rates, the structural domains of vinculin unfold at forces in the 5-15 pN range and rapidly refold when forces are reduced back to 1 pN. Thus, vinculin domains also have the potential to act as force dependent molecular switches, akin to those in talin and alpha-catenin. As with the force dependent switches in talin, the unfolding of these domains in vinculin introduces large extension changes in the vinculin cytoskeletal linkage up to 150 nm with 20-30 nm steps of unfolding. Modelling of the tension-dependent interactions of the unstructured vinculin linker region with a model protein containing two SH3 domains indicated that even unstructured protein regions can mediate force-dependent interactions with ligands, where the binding of a dual-SH3 model protein is predicted to be significantly suppressed by forces greater than 10 pN. Together, these findings suggest that vinculin has a complex mechanical response with force-dependent interaction sites, suggesting it also acts as a mechanotransducer, recruiting partners in response to force.

Item Type: Preprint
DOI/Identification number: 10.1101/2023.05.25.542235
Refereed: No
Other identifier:
Name of pre-print platform: bioRxiv
Additional information: For the purpose of open access, the author(s) has applied a Creative Commons Attribution (CC BY) licence to any Author Accepted Manuscript version arising.
Uncontrolled keywords: talin, vinculin, mechanobiology, cytoskeleton, integrins,
Subjects: Q Science > QH Natural history > QH301 Biology
Divisions: Divisions > Division of Natural Sciences > Biosciences
Funders: Biotechnology and Biological Sciences Research Council (
Cancer Research UK (
Depositing User: Ben Goult
Date Deposited: 25 May 2023 18:32 UTC
Last Modified: 20 Nov 2023 15:27 UTC
Resource URI: (The current URI for this page, for reference purposes)
Goult, Benjamin T:
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