Extracellular rigidity sensing by talin isoform-specific mechanical linkages.

Austen K, Ringer P, Mehlich A, Chrostek-Grashoff A, Kluger C, Klingner C, Sabass B, Zent R, Rief M, Grashoff C
Nat Cell Biol. 2015 17 (12): 1597-606

PMID: 26523364 · PMCID: PMC4662888 · DOI:10.1038/ncb3268

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.

MeSH Terms (23)

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

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