The mechanical response of vinculin

Liu, Xuyao, Wang, Yinan, Yao, Mingxi, Baker, Karen, Klapholz, Benjamin, Brown, Nicholas, Goult, Benjamin ORCID: 0000-0002-3438-2807 and Yan, Jie (2023) The mechanical response of vinculin. [Preprint]

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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
Uncontrolled Keywords:	1.1 Normal biological development and functioning, 1 Underpinning research
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User:	Symplectic Admin
Date Deposited:	13 Mar 2024 10:02
Last Modified:	15 Mar 2024 20:50
DOI:	10.1101/2023.05.25.542235
Related URLs:	Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3179299