Skip to main content
Kent Academic Repository

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.
Official URL:
https://doi.org/10.1101/2023.05.25.542235

Abstract

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: https://www.biorxiv.org/content/10.1101/2023.05.25...
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 (https://ror.org/00cwqg982)
Cancer Research UK (https://ror.org/054225q67)
Depositing User: Ben Goult
Date Deposited: 25 May 2023 18:32 UTC
Last Modified: 20 Nov 2023 15:27 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/101416 (The current URI for this page, for reference purposes)

University of Kent Author Information

Baker, Karen.

Creator's ORCID:
CReDIT Contributor Roles:

Goult, Benjamin T.

Creator's ORCID: https://orcid.org/0000-0002-3438-2807
CReDIT Contributor Roles:
  • Depositors only (login required):

Total unique views for this document in KAR since July 2020. For more details click on the image.