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The mechanical response of talin

Mingxi Yao, Benjamin T. Goult, Benjamin Klapholz, Xian Hu, Christopher P. Toseland, Yingjian Guo, Peiwen Cong, Michael P. Sheetz () and Jie Yan ()
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Mingxi Yao: Mechanobiology Institute, National University of Singapore
Benjamin T. Goult: School of Biosciences, University of Kent
Benjamin Klapholz: Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge
Xian Hu: Mechanobiology Institute, National University of Singapore
Christopher P. Toseland: School of Biosciences, University of Kent
Yingjian Guo: Mechanobiology Institute, National University of Singapore
Peiwen Cong: Mechanobiology Institute, National University of Singapore
Michael P. Sheetz: Mechanobiology Institute, National University of Singapore
Jie Yan: Mechanobiology Institute, National University of Singapore

Nature Communications, 2016, vol. 7, issue 1, 1-11

Abstract: Abstract Talin, a force-bearing cytoplasmic adapter essential for integrin-mediated cell adhesion, links the actin cytoskeleton to integrin-based cell–extracellular matrix adhesions at the plasma membrane. Its C-terminal rod domain, which contains 13 helical bundles, plays important roles in mechanosensing during cell adhesion and spreading. However, how the structural stability and transition kinetics of the 13 helical bundles of talin are utilized in the diverse talin-dependent mechanosensing processes remains poorly understood. Here we report the force-dependent unfolding and refolding kinetics of all talin rod domains. Using experimentally determined kinetics parameters, we determined the dynamics of force fluctuation during stretching of talin under physiologically relevant pulling speeds and experimentally measured extension fluctuation trajectories. Our results reveal that force-dependent stochastic unfolding and refolding of talin rod domains make talin a very effective force buffer that sets a physiological force range of only a few pNs in the talin-mediated force transmission pathway.

Date: 2016
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DOI: 10.1038/ncomms11966

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