title: The mechanical response of talin.
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.
authors.affiliation: Mechanobiology Institute, National University of Singapore, Singapore 117411, Singapore.
authors.forename: Mingxi
authors.identifier: 0000-0002-3905-8475
authors.initials: M
authors.lastname: Yao
authors.affiliation: School of Biosciences, University of Kent, Canterbury CT2 7NJ, UK.
authors.forename: Benjamin T
authors.identifier: 0000-0002-3438-2807
authors.initials: BT
authors.lastname: Goult
authors.affiliation: Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK.|Department of Physiology, Development and Neuroscience, University of Cambridge, Anatomy Building, Downing street, Cambridge CB2 3DY, UK.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Klapholz
authors.affiliation: Mechanobiology Institute, National University of Singapore, Singapore 117411, Singapore.
authors.forename: Xian
authors.initials: X
authors.lastname: Hu
authors.affiliation: School of Biosciences, University of Kent, Canterbury CT2 7NJ, UK.
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Toseland
authors.affiliation: Mechanobiology Institute, National University of Singapore, Singapore 117411, Singapore.
authors.forename: Yingjian
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Mechanobiology Institute, National University of Singapore, Singapore 117411, Singapore.
authors.forename: Peiwen
authors.initials: P
authors.lastname: Cong
authors.affiliation: Mechanobiology Institute, National University of Singapore, Singapore 117411, Singapore.|Department of Biological Sciences, Columbia University, New York, New York 10027, USA.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Sheetz
authors.affiliation: Mechanobiology Institute, National University of Singapore, Singapore 117411, Singapore.|Department of Physics, National University of Singapore, Singapore 117542, Singapore.|Centre for Bioimaging Sciences, National University of Singapore, Singapore 117546, Singapore.
authors.forename: Jie
authors.identifier: 0000-0002-8555-7291
authors.initials: J
authors.lastname: Yan
mesh_terms: D000818:Animals; D001665:Binding Sites; D001696:Biomechanical Phenomena; D003001:Cloning, Molecular; D010450:Endopeptidases / Q000737:chemistry; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D007700:Kinetics; D051379:Mice; D008958:Models, Molecular; D011485:Protein Binding; D017510:Protein Folding; D054730:Protein Interaction Domains and Motifs; D058849:Protein Refolding; D017433:Protein Structure, Secondary; D011993:Recombinant Fusion Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D000072760:Single Molecule Imaging / Q000379:methods*; D013314:Stress, Mechanical; D016608:Talin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D013816:Thermodynamics
chemical_list: D011993:Recombinant Fusion Proteins; D016608:Talin; C496077:Tln1 protein, mouse; D005982:Glutathione Transferase; D010450:Endopeptidases; C099488:TEV protease