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bioRxiv · 10.1101/2023.05.25.542235

The mechanical response of vinculin

Liu, X.·Wang, Y.·Yao, M.·Baker, K. B.·Klapholz, B.·Brown, N. H. T.·Goult, B. T.·Yan, J.
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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.

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Liu, X., Wang, Y., Yao, M., Baker, K. B., Klapholz, B., Brown, N. H. T., Goult, B. T., Yan, J.. 2023-05-25. The mechanical response of vinculin. https://doi.org/10.1101/2023.05.25.542235

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