The mechanical response of talin

Nat Commun. 2016 Jul 7:7:11966. doi: 10.1038/ncomms11966.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites
  • Biomechanical Phenomena
  • Cloning, Molecular
  • Endopeptidases / chemistry
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Gene Expression
  • Glutathione Transferase / genetics
  • Glutathione Transferase / metabolism
  • Kinetics
  • Mice
  • Models, Molecular
  • Protein Binding
  • Protein Folding
  • Protein Interaction Domains and Motifs
  • Protein Refolding
  • Protein Structure, Secondary
  • Recombinant Fusion Proteins / chemistry*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Single Molecule Imaging / methods*
  • Stress, Mechanical
  • Talin / chemistry*
  • Talin / genetics
  • Talin / metabolism
  • Thermodynamics

Substances

  • Recombinant Fusion Proteins
  • Talin
  • Tln1 protein, mouse
  • Glutathione Transferase
  • Endopeptidases
  • TEV protease