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

Oakes, Patrick W.; Beckham, Yvonne; Stricker, Jonathan; Gardel, Margaret L.

doi:10.1083/jcb.201107042

Cited by 292 publications

(368 citation statements)

References 52 publications

(114 reference statements)

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“…A similar dependence of shear tractions on substrate stiffness is predicted by the modelling framework used in the current study. It should be noted that, in the present study, significant tractions in the normal direction are where the cell has formed an approximately axisymmetric geometry, similar to that simulated here, the predicted orientations are found to be in agreement with experimentally observed dominant fibre bundles (Oakes et al 2012;Potter et al 1998) While the current study represents a step forward in the computational investigation of SF and FA behaviour of cells spread on elastic substrates, a number of limitations exist that should be considered in future studies. Experimental studies have shown that protrusion forces exerted by filopodia and lamellipodia during spreading can be ~ 5pN and ~20 pN (Cojoc et al 2007).…”

Section: Simulations Reveal Thatsupporting

confidence: 84%

“…FA formation is modulated by traction forces on the adhesion and the size of the adhesion increases with force (Tan et al 2003;Balaban et al 2001). FAs are typically observed experimentally at the end of SF bundles (Burridge et al 1988) and disrupting SF contractility has been shown to cause FAs to disappear (Oakes et al 2012). Previous attempts to simulate FA dynamics have not considered the coupling between active SF contractility and FA assembly (Shemesh et al 2005;Bruinsma 2005).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Cellular contractility and substrate elasticity: a numerical investigation of the actin cytoskeleton and cell adhesion

Ronan

Deshpande

McMeeking

et al. 2013

Biomech Model Mechanobiol

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Publication InformationRonan, William, Deshpande, Vikram S., McMeeking, Robert M., & McGarry, J. Patrick. (2014). Cellular contractility and substrate elasticity: a numerical investigation of the actin cytoskeleton and cell adhesion. Biomechanics found to alter the range of substrate stiffness that cause the most significant changes in stress fibre and focal adhesion formation. Furthermore, stress fibre and focal adhesion formation evolve as a cell spreads on a substrate and leading to the formation of bands of fibres leading from the cell periphery over the nucleus. Inhibiting the formation of FAs during cell spreading is found to limit stress fibre formation. The predictions of this mutually dependent material-interface framework are strongly supported by experimental observations of cells adhered to elastic substrates and offer insight into the interdependent biomechanical processes regulating stress fibre and focal adhesion formation.

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Section: Simulations Reveal Thatsupporting

confidence: 84%

Section: Introductionmentioning

confidence: 99%

Cellular contractility and substrate elasticity: a numerical investigation of the actin cytoskeleton and cell adhesion

Ronan

Deshpande

McMeeking

et al. 2013

Biomech Model Mechanobiol

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“…However, the speed of the patterning process is slow, making printing of large areas cumbersome and access to a specialized instrument is crucial. The two patterning methods are relevant for consideration because the size and shape of adhesive cue patterns influence the organization and distribution of biomechanical machineries that regulate cell migration 32,33 . Additionally, the limitation of the commercial microfluidic device employed here is that the channel length (1 μm) cannot be altered and so one cannot control the maximum steepness of the adhesive and soluble gradients.…”

Section: Discussionmentioning

confidence: 99%

Creating Adhesive and Soluble Gradients for Imaging Cell Migration with Fluorescence Microscopy

Ngalim

Magenau

Zhu

et al. 2013

JoVE

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Cells can sense and migrate towards higher concentrations of adhesive cues such as the glycoproteins of the extracellular matrix and soluble cues such as growth factors. Here, we outline a method to create opposing gradients of adhesive and soluble cues in a microfluidic chamber, which is compatible with live cell imaging. A copolymer of poly-L-lysine and polyethylene glycol (PLL-PEG) is employed to passivate glass coverslips and prevent non-specific adsorption of biomolecules and cells. Next, microcontact printing or dip pen lithography are used to create tracks of streptavidin on the passivated surfaces to serve as anchoring points for the biotinylated peptide arginine-glycine-aspartic acid (RGD) as the adhesive cue. A microfluidic device is placed onto the modified surface and used to create the gradient of adhesive cues (100% RGD to 0% RGD) on the streptavidin tracks. Finally, the same microfluidic device is used to create a gradient of a chemoattractant such as fetal bovine serum (FBS), as the soluble cue in the opposite direction of the gradient of adhesive cues. Video LinkThe video component of this article can be found at

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“…Pxn is used as the FA marker in this study, as its abundance in FAs is largely independent from myosin II activity 65 . This was used to generate a spatial mask to quantify and normalize local FAK activation as a function of myosin II activity, as has been done in previous studies 66,67 . An in-house built MATLAB script was used to quantify micrographs based on the morphometry and intensity of adhesions.…”

Section: Methodsmentioning

confidence: 99%

Dynamic catch of a Thy-1–α5β1+syndecan-4 trimolecular complex

Fiore

Chen

et al. 2014

Nat Commun

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Cancer cell adhesion to the vascular endothelium is a critical step of tumour metastasis. Endothelial surface molecule Thy-1 (CD90) is implicated in the metastatic process through its interactions with integrins and syndecans. However, how Thy-1 supports cell-cell adhesion in a dynamic mechanical environment is not known. Here we show that Thy-1 supports b 1 integrin-and syndecan-4 (Syn4)-mediated contractility-dependent mechanosignalling of melanoma cells. At the single-molecule level, Thy-1 is capable of independently binding a 5 b 1 integrin and syndecan-4 (Syn4) receptors. However, in the presence of both a 5 b 1 and Syn4, the two receptors bind cooperatively to Thy-1, to form a trimolecular complex. This trimolecular complex displays a unique phenomenon we coin 'dynamic catch', characterized by abrupt bond stiffening followed by the formation of catch bonds, where force prolongs the bond lifetime. Thus, we reveal a new class of trimolecular interactions where force strengthens the synergistic binding of two co-receptors and modulates downstream mechanosignalling.

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

Abstract: Lamellar actin architecture at adhesion sites may serve as a structural template that facilitates focal adhesion maturation over a wide range of tension.

Cited by 292 publications

References 52 publications

Cellular contractility and substrate elasticity: a numerical investigation of the actin cytoskeleton and cell adhesion

Cellular contractility and substrate elasticity: a numerical investigation of the actin cytoskeleton and cell adhesion

Creating Adhesive and Soluble Gradients for Imaging Cell Migration with Fluorescence Microscopy

Dynamic catch of a Thy-1–α5β1+syndecan-4 trimolecular complex

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