scholarly journals Nanopatterning reveals an ECM area threshold for focal adhesion assembly and force transmission that is regulated by integrin activation and cytoskeleton tension

2012 ◽  
Vol 125 (21) ◽  
pp. 5110-5123 ◽  
Author(s):  
S. R. Coyer ◽  
A. Singh ◽  
D. W. Dumbauld ◽  
D. A. Calderwood ◽  
S. W. Craig ◽  
...  
Keyword(s):  
Focal Adhesion ◽  
Force Transmission ◽  
Integrin Activation

Force-induced focal adhesion translocation: effects of force amplitude and frequency

2004 ◽  
Vol 287 (4) ◽  
pp. C954-C962 ◽  
Author(s):  
P. J. Mack ◽  
M. R. Kaazempur-Mofrad ◽  
H. Karcher ◽  
R. T. Lee ◽  
R. D. Kamm
Keyword(s):  
Tyrosine Kinase ◽  
Focal Adhesion ◽  
Magnetic Beads ◽  
Kinase Inhibitors ◽  
Kinase Inhibitor ◽  
Apical Cell ◽  
Force Transmission ◽  
Shear Forces ◽  
Apical Cell Membrane ◽  
Adhesion Sites

Vascular endothelial cells rapidly transduce local mechanical forces into biological signals through numerous processes including the activation of focal adhesion sites. To examine the mechanosensing capabilities of these adhesion sites, focal adhesion translocation was monitored over the course of 5 min with GFP-paxillin while applying nN-level magnetic trap shear forces to the cell apex via integrin-linked magnetic beads. A nongraded steady-load threshold for mechanotransduction was established between 0.90 and 1.45 nN. Activation was greatest near the point of forcing (<7.5 μm), indicating that shear forces imposed on the apical cell membrane transmit nonuniformly to the basal cell surface and that focal adhesion sites may function as individual mechanosensors responding to local levels of force. Results from a continuum, viscoelastic finite element model of magnetocytometry that represented experimental focal adhesion attachments provided support for a nonuniform force transmission to basal surface focal adhesion sites. To further understand the role of force transmission on focal adhesion activation and dynamics, sinusoidally varying forces were applied at 0.1, 1.0, 10, and 50 Hz with a 1.45 nN offset and a 2.25 nN maximum. At 10 and 50 Hz, focal adhesion activation did not vary with spatial location, as observed for steady loading, whereas the response was minimized at 1.0 Hz. Furthermore, applying the tyrosine kinase inhibitors genistein and PP2, a specific Src family kinase inhibitor, showed tyrosine kinase signaling has a role in force-induced translocation. These results highlight the mutual importance of force transmission and biochemical signaling in focal adhesion mechanotransduction.

scholarly journals Tension is required but not sufficient for focal adhesion maturation without a stress fiber template

2012 ◽  
Vol 196 (3) ◽  
pp. 363-374 ◽  
Author(s):  
Patrick W. Oakes ◽  
Yvonne Beckham ◽  
Jonathan Stricker ◽  
Margaret L. Gardel
Keyword(s):  
Focal Adhesion ◽  
Myosin Ii ◽  
Focal Adhesions ◽  
Stress Fiber ◽  
Matrix Remodeling ◽  
Force Transmission ◽  
Fiber Assembly ◽  
Wide Range ◽  
Structural Template

Focal adhesion composition and size are modulated in a myosin II–dependent maturation process that controls adhesion, migration, and matrix remodeling. As myosin II activity drives stress fiber assembly and enhanced tension at adhesions simultaneously, the extent to which adhesion maturation is driven by tension or altered actin architecture is unknown. We show that perturbations to formin and α-actinin 1 activity selectively inhibited stress fiber assembly at adhesions but retained a contractile lamella that generated large tension on adhesions. Despite relatively unperturbed adhesion dynamics and force transmission, impaired stress fiber assembly impeded focal adhesion compositional maturation and fibronectin remodeling. Finally, we show that compositional maturation of focal adhesions could occur even when myosin II–dependent cellular tension was reduced by 80%. We propose that stress fiber assembly at the adhesion site serves as a structural template that facilitates adhesion maturation over a wide range of tensions. This work identifies the essential role of lamellar actin architecture in adhesion maturation.

scholarly journals The mechanism of force transmission at bacterial focal adhesion complexes

Nature ◽  
2016 ◽  
Vol 539 (7630) ◽  
pp. 530-535 ◽  
Author(s):  
Laura M. Faure ◽  
Jean-Bernard Fiche ◽  
Leon Espinosa ◽  
Adrien Ducret ◽  
Vivek Anantharaman ◽  
...  
Keyword(s):  
Focal Adhesion ◽  
Force Transmission

scholarly journals Correction: Talin tension sensor reveals novel features of focal adhesion force transmission and mechanosensitivity

2016 ◽  
Vol 214 (2) ◽  
pp. 231-231 ◽  
Author(s):  
Abhishek Kumar ◽  
Mingxing Ouyang ◽  
Koen Van den Dries ◽  
Ewan James McGhee ◽  
Keiichiro Tanaka ◽  
...  
Keyword(s):  
Focal Adhesion ◽  
Adhesion Force ◽  
Force Transmission ◽  
Tension Sensor

scholarly journals Focal Adhesion Kinase Modulates Cell Adhesion Strengthening via Integrin Activation

2009 ◽  
Vol 20 (9) ◽  
pp. 2508-2519 ◽  
Author(s):  
Kristin E. Michael ◽  
David W. Dumbauld ◽  
Kellie L. Burns ◽  
Steven K. Hanks ◽  
Andrés J. García
Keyword(s):  
Cell Migration ◽  
Cell Adhesion ◽  
Focal Adhesion Kinase ◽  
Focal Adhesion ◽  
Human Fibroblasts ◽  
Inducible Promoter ◽  
Time Dependent ◽  
Integrin Activation ◽  
Nonreceptor Tyrosine Kinase ◽  
Adhesive Forces

Focal adhesion kinase (FAK) is an essential nonreceptor tyrosine kinase regulating cell migration, adhesive signaling, and mechanosensing. Using FAK-null cells expressing FAK under an inducible promoter, we demonstrate that FAK regulates the time-dependent generation of adhesive forces. During the early stages of adhesion, FAK expression in FAK-null cells enhances integrin activation to promote integrin binding and, hence, the adhesion strengthening rate. Importantly, FAK expression regulated integrin activation, and talin was required for the FAK-dependent effects. A role for FAK in integrin activation was confirmed in human fibroblasts with knocked-down FAK expression. The FAK autophosphorylation Y397 site was required for the enhancements in adhesion strengthening and integrin-binding responses. This work demonstrates a novel role for FAK in integrin activation and the time-dependent generation of cell–ECM forces.

scholarly journals Force-independent interactions of talin and vinculin govern integrin-mediated mechanotransduction

2019 ◽  
Author(s):  
Paul Atherton ◽  
Franziska Lausecker ◽  
Alexandre Carisey ◽  
Andrew Gilmore ◽  
David Critchley ◽  
...  
Keyword(s):  
Focal Adhesion ◽  
Critical Role ◽  
Traction Force ◽  
Full Length ◽  
Mitochondrial Targeting ◽  
Integrin Activation ◽  
Traction Forces ◽  
The Matrix ◽  
Core Components ◽  
Dynamic Link

Talin, vinculin and paxillin are core components of the dynamic link between integrins and actomyosin. Here we study the mechanisms that mediate their activation and association using a mitochondrial-targeting assay, structure-based mutants, and advanced microscopy. As expected, full-length vinculin and talin are auto-inhibited and do not interact with each other in this state. Contrary to previous models that propose a critical role for forces driving talin-vinculin association, our data show that force-independent relief of auto-inhibition is sufficient to mediate their tight interaction. Interestingly, paxillin can bind to both talin and vinculin when either is inactive. Further experiments demonstrate that adhesions containing paxillin and vinculin can form without talin following integrin activation. However, these are largely deficient in exerting traction forces to the matrix. Our observations lead to a model whereby paxillin contributes to talin and vinculin recruitment into nascent adhesions. Activation of the talin-vinculin axis subsequently leads to the engagement with the traction force-machinery and focal adhesion maturation.

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