Extracellular rigidity sensing by talin isoform-specific mechanical linkages

Nat Cell Biol. 2015 Dec;17(12):1597-606. doi: 10.1038/ncb3268. Epub 2015 Nov 2.

Abstract

The ability of cells to adhere and sense differences in tissue stiffness is crucial for organ development and function. The central mechanisms by which adherent cells detect extracellular matrix compliance, however, are still unknown. Using two single-molecule-calibrated biosensors that allow the analysis of a previously inaccessible but physiologically highly relevant force regime in cells, we demonstrate that the integrin activator talin establishes mechanical linkages following cell adhesion, which are indispensable for cells to probe tissue stiffness. Talin linkages are exposed to a range of piconewton forces and bear, on average, 7-10 pN during cell adhesion depending on their association with F-actin and vinculin. Disruption of talin's mechanical engagement does not impair integrin activation and initial cell adhesion but prevents focal adhesion reinforcement and thus extracellular rigidity sensing. Intriguingly, talin mechanics are isoform specific so that expression of either talin-1 or talin-2 modulates extracellular rigidity sensing.

Publication types

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

MeSH terms

  • Actin Cytoskeleton / metabolism
  • Actins / metabolism
  • Animals
  • Biosensing Techniques / methods*
  • Blotting, Western
  • Cell Adhesion
  • Cells, Cultured
  • Extracellular Matrix / metabolism*
  • Fibroblasts / cytology
  • Fibroblasts / metabolism
  • Fluorescence Resonance Energy Transfer
  • Focal Adhesions / metabolism*
  • Luminescent Proteins / genetics
  • Luminescent Proteins / metabolism
  • Mechanical Phenomena
  • Mice, Knockout
  • Mice, Transgenic
  • Microfilament Proteins / genetics
  • Microfilament Proteins / metabolism
  • Microscopy, Confocal
  • Microscopy, Fluorescence
  • Optical Tweezers
  • Peptides / genetics
  • Peptides / metabolism
  • Protein Binding
  • Talin / genetics
  • Talin / metabolism*
  • Vinculin / genetics
  • Vinculin / metabolism

Substances

  • Actins
  • Luminescent Proteins
  • Microfilament Proteins
  • Peptides
  • TLN2 protein, mouse
  • Talin
  • talin protein, mouse
  • villin
  • Vinculin