Integrins in mechanotransduction

Ross, Tyler D; Coon, Brian Bg; Yun, Sanguk; Baeyens, Nicolas; Tanaka, Keiichiro; Ouyang, Mingxing; Schwartz, Martin A.

doi:10.1016/j.ceb.2013.05.006

Cited by 284 publications

(238 citation statements)

References 52 publications

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“…This is mediated by an increase in integrin clustering and in the size and number of integrin-based focal adhesions (Califano and Reinhart-King, 2010;van Geemen et al, 2014). Integrins sense the stiffness of the underlying substrate and translate mechanical forces into endothelial signaling to induce F-actin remodeling and myosin-based contraction (Oakes and Gardel, 2014;Roca-Cusachs et al, 2012;Ross et al, 2013). Human ECs on stiff matrices show increased numbers of focal adhesions and F-actin stress fibers, similar to what was observed in rigid human arteries (van Geemen et al, 2014).…”

Section: Mechanotransduction In Ecs Substrate Stiffness Controls Endosupporting

confidence: 51%

“…This recruitment induces a local increase in the density of the F-actin network at the selectin clusters, which is likely to result in local EC stiffening and, thus, provides an improved platform for anchoring of selectins to the F-actin network in order to resist shear force, similar to what has been described for integrins (Roca-Cusachs et al, 2012;Ross et al, 2013). By contrast, destabilization the endothelial F-actin network with cytochalasin B inhibits clustering und function of selectins, which is indicative for a positive-feedback loop (Wojciak-Stothard et al, 1999).…”

Section: Box 1 Mechanotransduction In Inflammatory Diseasementioning

confidence: 85%

“…ECs) and sense local EC stiffness through ventral filopodia or invadosome-like protrusions Martinelli et al, 2014;Schaefer et al, 2014;Shulman et al, 2009). The mechanosensitive response of leukocytes to substrate stiffness is mediated by their integrins, which are force-generating mechanoreceptors (Roca-Cusachs et al, 2012;Ross et al, 2013). Integrin-derived forces are translated into (biochemical) signaling events within the leukocyte, including the recruitment of actin-binding or signaling proteins to the integrin cytoplasmic tail.…”

Section: Mechanotransduction In Leukocytesmentioning

confidence: 99%

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Cell-stiffness-induced mechanosignaling – a key driver of leukocyte transendothelial migration

Schaefer

Hordijk

2015

Journal of Cell Science

103

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The breaching of cellular and structural barriers by migrating cells is a driving factor in development, inflammation and tumor cell metastasis. One of the most extensively studied examples is the extravasation of activated leukocytes across the vascular endothelium, the inner lining of blood vessels. Each step of this leukocyte transendothelial migration (TEM) process is regulated by distinct endothelial adhesion receptors such as the intercellular adhesion molecule 1 (ICAM1). Adherent leukocytes exert force on these receptors, which sense mechanical cues and transform them into localized mechanosignaling in endothelial cells. In turn, the function of the mechanoreceptors is controlled by the stiffness of the endothelial cells and of the underlying substrate representing a positive-feedback loop. In this Commentary, we focus on the mechanotransduction in leukocytes and endothelial cells, which is induced in response to variations in substrate stiffness. Recent studies have described the first key proteins involved in these mechanosensitive events, allowing us to identify common regulatory mechanisms in both cell types. Finally, we discuss how endothelial cell stiffness controls the individual steps in the leukocyte TEM process. We identify endothelial cell stiffness as an important component, in addition to locally presented chemokines and adhesion receptors, which guides leukocytes to sites that permit TEM.

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Section: Mechanotransduction In Ecs Substrate Stiffness Controls Endosupporting

confidence: 51%

Section: Box 1 Mechanotransduction In Inflammatory Diseasementioning

confidence: 85%

Section: Mechanotransduction In Leukocytesmentioning

confidence: 99%

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Cell-stiffness-induced mechanosignaling – a key driver of leukocyte transendothelial migration

Schaefer

Hordijk

2015

Journal of Cell Science

103

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“…[42][43][44] By controlling both the perception of mechanical cues and the execution of the cellular response, integrin-based adhesions are thought to play a crucial role in mechanotransduction. Indeed, FAs have been shown to respond to substrate mechanical properties, thereby regulating cellular processes.…”

Section: Podosomes As Mechanotransducersmentioning

confidence: 99%

Spatiotemporal organization and mechanosensory function of podosomes

Dries

Bolomini-Vittori

Cambi³

2014

Cell Adhesion & Migration

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“…28 Integrins physically bridge the cellular cytoskeleton with the extracellular matrix, and accordingly experience pN forces. [15] Assays that allow for screening of compounds that modulate integrin tension are of potential significance.First, we quantified integrin-mediated denaturation of immobilized DNA duplexes. 5′-Cy3B, 3′-biotin labeled complement was hybridized to the primer (Figure 2A).…”

mentioning

confidence: 99%

Mechanically Induced Catalytic Amplification Reaction for Readout of Receptor‐Mediated Cellular Forces

et al. 2016

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Mechanics play a fundamental role in cell biology, but detecting piconewton forces is challenging due to the lack of accessible and high throughput assays. Herein we report the mechanicallyinduced catalytic amplification reaction (MCR) for readout of receptor-mediated forces in cells. Mechanically labile DNA duplexes presenting ligands are surface immobilized such that specific receptor forces denature the duplex and thus expose a blocked primer. Amplification of primers is achieved using an isothermal polymerization reaction and quantified by fluorescence readout. As a proof-of-concept, the assay was used to test the activity of a mechano-modulatory drug and integrin adhesion receptor antibodies. To the best of our knowledge, this is the first example of a catalytic reaction triggered in response to molecular piconewton forces. The MCR may transform the field of mechanobiology by providing a new facile tool to detect receptor-specific mechanics with the convenience of the PCR. Graphical AbstractHerein we report the mechanically-induced catalytic amplification reaction (MCR) for readout of receptor-mediated forces in cells. To the best of our knowledge, this is the first example of a catalytic reaction triggered in response to molecular piconewton forces.Correspondence to: Khalid Salaita. Supporting information for this article is given via a link at the end of the document. Coupling between mechanical forces and chemistry at interfaces plays a profound role in biological processes ranging from biofilm formation to stem cell differentiation, and wound healing. [1] To understand these types of chemo-mechanical coupling processes, it is necessary to develop methods to quantify cellular forces. This is challenging because molecular forces in biochemical processes are transient and tend to range from ~1-100 pN, which is sufficient to drive conformational changes in proteins but insufficient to dissociate covalent bonds. [2] Therefore, forces in biochemical systems are difficult to detect and map. HHS Public AccessWe previously developed molecular tension-based fluorescence microscopy (MTFM) to image forces transmitted by cell surface receptors in living cells. [3] The initial tension probes were comprised of an extendable polyethylene glycol (PEG) spring, flanked by a fluorophore and a spectroscopically-matched quencher. [4] pN forces extend the mean end-toend distance of the polymer, which reduces energy transfer through an R −6 distancedependent relationship. Next generation probes utilized oligonucleotides, [5] elastin like polypeptides, [6] and engineered proteins [7] , and also employed gold nanoparticle quenchers to extend energy transfer distances and enhanced sensitivity. [7][8] Nonetheless, the sensitivity of MTFM is limited due to the energy transfer-based readout and the transient nature of cellular forces. For example, current probes require high-end microscopy systems with single-photon counting EMCCDs coupled with high-numerical aperture (NA) objectives to detect changes in energy transfer ...

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Integrins in mechanotransduction

Cited by 284 publications

References 52 publications

Cell-stiffness-induced mechanosignaling – a key driver of leukocyte transendothelial migration

Cell-stiffness-induced mechanosignaling – a key driver of leukocyte transendothelial migration

Spatiotemporal organization and mechanosensory function of podosomes

Mechanically Induced Catalytic Amplification Reaction for Readout of Receptor‐Mediated Cellular Forces

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