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 Talin tension sensor reveals novel features of focal adhesion force transmission and mechanosensitivity

2016 ◽  
Vol 213 (3) ◽  
pp. 371-383 ◽  
Author(s):  
Abhishek Kumar ◽  
Mingxing Ouyang ◽  
Koen Van den Dries ◽  
Ewan James McGhee ◽  
Keiichiro Tanaka ◽  
...  
Keyword(s):  
Adhesion Force ◽  
Focal Adhesions ◽  
Actin Binding ◽  
Force Transmission ◽  
C Terminus ◽  
Tension Sensor ◽  
Cellular Mechanosensing ◽  
The Difference ◽  
Development And Validation ◽  
Actin Binding Site

Integrin-dependent adhesions are mechanosensitive structures in which talin mediates a linkage to actin filaments either directly or indirectly by recruiting vinculin. Here, we report the development and validation of a talin tension sensor. We find that talin in focal adhesions is under tension, which is higher in peripheral than central adhesions. Tension on talin is increased by vinculin and depends mainly on actin-binding site 2 (ABS2) within the middle of the rod domain, rather than ABS3 at the far C terminus. Unlike vinculin, talin is under lower tension on soft substrates. The difference between central and peripheral adhesions requires ABS3 but not vinculin or ABS2. However, differential stiffness sensing by talin requires ABS2 but not vinculin or ABS3. These results indicate that central versus peripheral adhesions must be organized and regulated differently, and that ABS2 and ABS3 have distinct functions in spatial variations and stiffness sensing. Overall, these results shed new light on talin function and constrain models for cellular mechanosensing.

scholarly journals Dystrophin modulates focal adhesion tension and YAP-mediated mechanotransduction

2021 ◽  
Author(s):  
Maria Paz Ramirez ◽  
Michael JM Anderson ◽  
Lauren J Sundby ◽  
Anthony R Hagerty ◽  
Sophia J Wenthe ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Muscular Dystrophy ◽  
Focal Adhesion ◽  
Adhesion Force ◽  
Muscle Protein ◽  
Focal Adhesions ◽  
Becker Muscular Dystrophy ◽  
Missense Mutations ◽  
Force Transmission ◽  
Cell Membrane Stability

Dystrophin is an essential muscle protein that contributes to cell membrane stability by linking the actin cytoskeleton to the extracellular matrix. The absence or impaired function of dystrophin causes muscular dystrophy. Focal adhesions are mechanosensitive adhesion complexes that also connect the cytoskeleton to the extracellular matrix. However, the interplay between dystrophin and focal adhesion force transmission has not been investigated. Using a bioluminescent tension sensor, we measured focal adhesion tension in transgenic C2C12 myoblasts expressing wild type (WT) dystrophin, a non-pathogenic SNP (I232M), or two missense mutations associated with Duchenne (L54R), or Becker muscular dystrophy (L172H). We found that myoblasts expressing WT or nonpathogenic I232M dystrophin showed increased focal adhesion tension compared to non-transgenic myoblasts, while myoblasts expressing L54R or L172H dystrophin presented with decreased focal adhesion tension. Moreover, myoblasts expressing L54R or L172H dystrophin showed decreased YAP activation and exhibited slower and less directional migration compared to cells expressing WT or I232M dystrophin. Our results suggest that disease-causing missense mutations in dystrophin may disrupt a cellular tension sensing pathway in dystrophic skeletal muscle.

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 Evaluation of the Correlation between Focal Adhesion Kinase Phosphorylation and Cell Adhesion Force Using “DEP” Technology

Sensors ◽  
2012 ◽  
Vol 12 (5) ◽  
pp. 5951-5965 ◽  
Author(s):  
Chyung Ay ◽  
Chih-Chang Yeh ◽  
Min-Chih Hsu ◽  
Huaang-Youh Hurng ◽  
Philip Chi Lip Kwok ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Focal Adhesion Kinase ◽  
Focal Adhesion ◽  
Adhesion Force ◽  
Focal Adhesion Kinase Phosphorylation ◽  
Kinase Phosphorylation

scholarly journals An intact keratin network is crucial for mechanical integrity and barrier function in keratinocyte cell sheets

2019 ◽  
Author(s):  
Susanne Karsch ◽  
Fanny Büchau ◽  
Thomas M. Magin ◽  
Andreas Janshoff
Keyword(s):  
Barrier Function ◽  
Time Course ◽  
Mechanical Response ◽  
Adhesion Force ◽  
Cell Junctions ◽  
Force Transmission ◽  
Cell Sheets ◽  
Mechanical Integrity ◽  
Barrier Formation ◽  
Mechanical Homeostasis

AbstractThe isotype-specific composition of the keratin cytoskeleton is important for strong adhesion, force resilience, and barrier function of the epidermis. However, the mechanisms by which keratins regulate these functions are still incompletely understood. In this study, the role and significance of the keratin network for mechanical integrity, force transmission, and barrier formation were analyzed in murine keratinocytes. Following the time-course of single-cell wounding, wildtype (WT) cells slowly closed the gap in a collective fashion involving tightly connected neighboring cells. In contrast, the mechanical response of neighboring cells was compromised in keratin-deficient cells, causing an increased wound area initially and an inefficient overall wound closure. Furthermore, the loss of the keratin network led to impaired, fragmented cell-cell junctions and triggered a profound change in the overall cellular actomyosin architecture. Electrical cell-substrate impedance sensing of cell junctions revealed a dysfunctional barrier in knockout (Kty−/−) compared to WT cells. These findings demonstrate that Kty−/− cells display a novel phenotype characterized by loss of mechanocoupling and failure to form a functional barrier. Re-expression of K5/K14 rescued the barrier defect to a significant extent and reestablished the mechanocoupling with remaining discrepancies likely due to the low abundance of keratins in that setting. Our study reveals the major role of the keratin network for mechanical homeostasis and barrier functionality in keratinocyte layers.

scholarly journals Actin flow-dependent and -independent force transmission through integrins

2020 ◽  
Vol 117 (51) ◽  
pp. 32413-32422
Author(s):  
Tristan P. Driscoll ◽  
Sang Joon Ahn ◽  
Billy Huang ◽  
Abhishek Kumar ◽  
Martin A. Schwartz
Keyword(s):  
Binding Site ◽  
Focal Adhesion ◽  
Protein Interactions ◽  
Flow Speed ◽  
Substrate Stiffness ◽  
Actin Binding ◽  
Force Transmission ◽  
Force Transfer ◽  
Independent Mechanism ◽  
Actin Binding Site

Integrin-dependent adhesions mediate reciprocal exchange of force and information between the cell and the extracellular matrix. These effects are attributed to the “focal adhesion clutch,” in which moving actin filaments transmit force to integrins via dynamic protein interactions. To elucidate these processes, we measured force on talin together with actin flow speed. While force on talin in small lamellipodial adhesions correlated with actin flow, talin tension in large adhesions further from the cell edge was mainly flow-independent. Stiff substrates shifted force transfer toward the flow-independent mechanism. Flow-dependent force transfer required talin’s C-terminal actin binding site, ABS3, but not vinculin. Flow-independent force transfer initially required vinculin and at later times the central actin binding site, ABS2. Force transfer through integrins thus occurs not through a continuous clutch but through a series of discrete states mediated by distinct protein interactions, with their ratio modulated by substrate stiffness.

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