title: All Subdomains of the Talin Rod Are Mechanically Vulnerable and May Contribute To Cellular Mechanosensing.
abstract: Although the relevance of mechanotransduction in cell signaling is currently appreciated, the mechanisms that drive this process remain largely unknown. Mechanical unfolding of proteins may trigger distinct downstream signals in cells, providing a mechanism for cellular mechanotransduction. Force-induced unfolding of talin, a prominent focal adhesion protein, has been demonstrated previously for a small portion of its rod domain. Here, using single-molecule atomic force microscopy (smAFM), we show that the entire talin rod can be unfolded by mechanical extension, over a physiological range of forces between 10 and 40 pN. We also demonstrate, through a combination of smAFM and steered molecular dynamics, that the different bundles within the talin rod exhibit a distinct hierarchy of mechanical stability. These results provide a mechanism by which different force conditions within the cell control a graduated unfolding of the talin rod. Mechanical unfolding of the rod subdomains, and the subsequent effect on talin's binding interactions, would allow for a finely tuned cellular response to internally or externally applied forces.
authors.affiliation: Cellular and Molecular Biomechanics Laboratory, Department of Bioengineering, Imperial College London , London SW7 2AZ, United Kingdom.
authors.forename: Alexander William M
authors.initials: AW
authors.lastname: Haining
authors.affiliation: BioMediTech, University of Tampere , Biokatu 6, FI-33520 Tampere, Finland.|Fimlab Laboratories , Biokatu 4, FI-33520 Tampere, Finland.
authors.forename: Magdaléna
authors.initials: M
authors.lastname: von Essen
authors.affiliation: Cellular and Molecular Biomechanics Laboratory, Department of Bioengineering, Imperial College London , London SW7 2AZ, United Kingdom.
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Attwood
authors.affiliation: BioMediTech, University of Tampere , Biokatu 6, FI-33520 Tampere, Finland.|Fimlab Laboratories , Biokatu 4, FI-33520 Tampere, Finland.
authors.forename: Vesa P
authors.initials: VP
authors.lastname: Hytönen
authors.affiliation: Cellular and Molecular Biomechanics Laboratory, Department of Bioengineering, Imperial College London , London SW7 2AZ, United Kingdom.
authors.forename: Armando
authors.initials: A
authors.lastname: Del Río Hernández
mesh_terms: D022001:Focal Adhesions; D040542:Mechanotransduction, Cellular; D018625:Microscopy, Atomic Force; D011485:Protein Binding; D016608:Talin
chemical_list: D016608:Talin
keywords: mechanobiology; mechanotransduction; protein mechanostability; single-molecule force spectroscopy; steered molecular dynamics