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  Extracellular rigidity sensing by talin isoform-specific mechanical linkages

Austen, K., Ringer, P., Mehlich, A., Chrostek-Grashoff, A., Kluger, C., Klingner, C., et al. (2015). Extracellular rigidity sensing by talin isoform-specific mechanical linkages. NATURE CELL BIOLOGY, 17(12), 1597-1606. doi:10.1038/ncb3268.

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 Creators:
Austen, Katharina1, Author           
Ringer, Pia1, Author           
Mehlich, Alexander2, Author
Chrostek-Grashoff, Anna1, Author           
Kluger, Carleen1, Author           
Klingner, Christoph1, Author           
Sabass, Benedikt2, Author
Zent, Roy2, Author
Rief, Matthias2, Author
Grashoff, Carsten1, Author           
Affiliations:
1Grashoff, Carsten / Molecular Mechanotransduction, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565150              
2external, ou_persistent22              

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Free keywords: VINCULIN BINDING; FOCAL ADHESIONS; NANOSCALE ARCHITECTURE; CELL-MIGRATION; E-CADHERIN; FORCES; INTEGRIN; MECHANOTRANSDUCTION; REVEALS; TENSION
 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.

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Language(s): eng - English
 Dates: 2015
 Publication Status: Published in print
 Pages: 10
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: ISI: 000365932300012
DOI: 10.1038/ncb3268
 Degree: -

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Title: NATURE CELL BIOLOGY
Source Genre: Journal
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Publ. Info: MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND : NATURE PUBLISHING GROUP
Pages: - Volume / Issue: 17 (12) Sequence Number: - Start / End Page: 1597 - 1606 Identifier: ISSN: 1465-7392