title: Extracellular rigidity sensing by talin isoform-specific mechanical linkages.
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.
authors.affiliation: Max Planck Institute of Biochemistry, Group of Molecular Mechanotransduction, Martinsried D-82152, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Austen
authors.affiliation: Max Planck Institute of Biochemistry, Group of Molecular Mechanotransduction, Martinsried D-82152, Germany.
authors.forename: Pia
authors.initials: P
authors.lastname: Ringer
authors.affiliation: Technical University of Munich, Physics Department E22, Garching D-85748, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Mehlich
authors.affiliation: Max Planck Institute of Biochemistry, Group of Molecular Mechanotransduction, Martinsried D-82152, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Chrostek-Grashoff
authors.affiliation: Max Planck Institute of Biochemistry, Group of Molecular Mechanotransduction, Martinsried D-82152, Germany.
authors.forename: Carleen
authors.initials: C
authors.lastname: Kluger
authors.affiliation: Max Planck Institute of Biochemistry, Group of Molecular Mechanotransduction, Martinsried D-82152, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Klingner
authors.affiliation: Princeton University, Department of Mechanical &Aerospace Engineering, Princeton, New Jersey 08544, USA.
authors.forename: Benedikt
authors.initials: B
authors.lastname: Sabass
authors.affiliation: Vanderbilt University, Division of Nephrology, Department of Medicine, Nashville, Tennessee 37232, USA.
authors.forename: Roy
authors.initials: R
authors.lastname: Zent
authors.affiliation: Technical University of Munich, Physics Department E22, Garching D-85748, Germany.|Munich Centre for Integrated Protein Science, Munich D-81377, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Rief
authors.affiliation: Max Planck Institute of Biochemistry, Group of Molecular Mechanotransduction, Martinsried D-82152, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Grashoff
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000199:Actins / Q000378:metabolism; D000818:Animals; D015374:Biosensing Techniques / Q000379:methods*; D015153:Blotting, Western; D002448:Cell Adhesion; D002478:Cells, Cultured; D005109:Extracellular Matrix / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D031541:Fluorescence Resonance Energy Transfer; D022001:Focal Adhesions / Q000378:metabolism*; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D055595:Mechanical Phenomena; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D052898:Optical Tweezers; D010455:Peptides / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D016608:Talin / Q000235:genetics / Q000378:metabolism*; D016596:Vinculin / Q000235:genetics / Q000378:metabolism
chemical_list: D000199:Actins; D008164:Luminescent Proteins; D008840:Microfilament Proteins; D010455:Peptides; C518833:TLN2 protein, mouse; D016608:Talin; C496077:Tln1 protein, mouse; C026615:villin; D016596:Vinculin