Lateral spacing of integrin ligands influences cell spreading and focal adhesion assembly

Cavalcanti‐Adam, Elisabetta Ada; Micoulet, Alexandre; Blümmel, Jacques; Auernheimer, Jörg; Kessler, Horst; Spatz, Joachim P.

doi:10.1016/j.ejcb.2005.09.011

Cited by 342 publications

(296 citation statements)

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“…These adhesion complexes permit cells to sense multiple extracellular signals that specify the chemical identity, geometry and physical properties of the ECM 4,5 . Thus, cells behave differently on two-and three-dimensional matrices 6 , distinguish between different ECM components 7 , can detect differences in adhesive ligand density 8 , and respond to mechanical perturbation and surface rigidity 9,10 . …”

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confidence: 99%

Functional atlas of the integrin adhesome

Zaidel-Bar¹,

Itzkovitz²,

et al. 2007

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A detailed depiction of the 'integrin adhesome', consisting of a complex network of 156 components linked together and modified by 690 interactions is presented. Different views of the network reveal several functional 'subnets' that are involved in switching on or off many of the molecular interactions within the network, consequently affecting cell adhesion, migration and cytoskeletal organization. Examination of the adhesome network motifs reveals a relatively small number of key motifs, dominated by three-component complexes in which a scaffolding molecule recruits both a signalling molecule and its downstream target. We discuss the role of the different network modules in regulating the structural and signalling functions of cell-matrix adhesions. Top-down and bottom-up approaches for studying the integrin adhesomeCell-extracellular matrix (ECM) interactions are mediated through specialized subcellular sites that contain specific adhesion receptors, cytoskeletal elements and a wide variety of interconnecting adaptor proteins [1][2][3] . These adhesion complexes permit cells to sense multiple extracellular signals that specify the chemical identity, geometry and physical properties of the ECM 4,5 . Thus, cells behave differently on two-and three-dimensional matrices 6 , distinguish between different ECM components 7 , can detect differences in adhesive ligand density 8 , and respond to mechanical perturbation and surface rigidity 9,10 . Competing Financial Interests:The authors declare no competing financial interests.Website -www.adhesome.org contains the adhesome database of components and interactions with an interface that allows dynamical navigation between hyperlinked subnets created for each component and for many network motifs within the adhesome network.Publisher's Disclaimer: Disclaimer: Nature Publishing Group has a collaboration with the Cell Migration Consortium for the creation and maintenance of the Cell Migration gateway (http://www.cellmigration.org/), but has no role in generating or curating the Cell Migration Consortium database content. As always, Nature Cell Biology Editors have been fully independent and solely responsible for the editorial content and peer review of this Analysis article. NIH Public Access Author ManuscriptNat Cell Biol. Author manuscript; available in PMC 2009 August 31. Published in final edited form as:Nat Cell Biol. 2007 August ; 9(8): 858-867. doi:10.1038/ncb0807-858. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptTo understand the mechanisms underlying these diverse responses, in-depth characterization of individual proteins or pathways 11,12 , and collection of information about multiple components that concertedly form the presumed adhesome 13,14 , have been undertaken. Each of these approaches has limitations, and individually is unlikely to explain how the adhesion machinery senses environmental cues and responds to them. However, combining data from the two approaches could produce new mechanistic insights into the structu...

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confidence: 99%

Functional atlas of the integrin adhesome

Zaidel-Bar¹,

Itzkovitz²,

et al. 2007

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“…Decreasing the size of RGD-functionalized gold squares under 1 mm 2 results in poor recruitment of a5b1-integrin, altered actin assembly and a decreased rate of cell migration [40]. Decreasing adhesive spot density until a lateral spacing of 73 nm between integrin binding sites (RGD-functionalized gold nanoparticles 6 nm in diameter) inhibits focal contact formation [41]. Uniform distribution of RGD on functionalized substrates allows for cell adhesion when overcoming a threshold level depending on materials, bioconjugation and cell type.…”

Section: Molecular Cue-mediated Crosstalkmentioning

confidence: 99%

Determinants of cell–material crosstalk at the interface: towards engineering of cell instructive materials

Ventre

Causa

Netti

2012

J. R. Soc. Interface.

158

153

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The development of novel biomaterials able to control cell activities and direct their fate is warranted for engineering functional biological tissues, advanced cell culture systems, single-cell diagnosis as well as for cell sorting and differentiation. It is well established that crosstalk at the cell–material interface occurs and this has a profound influence on cell behaviour. However, the complete deciphering of the cell–material communication code is still far away. A variety of material surface properties have been reported to affect the strength and the nature of the cell–material interactions, including biological cues, topography and mechanical properties. Novel experimental evidence bears out the hypothesis that these three different signals participate in the same material–cytoskeleton crosstalk pathway via adhesion plaque formation dynamics. In this review, we present the relevant findings on material-induced cell response along with the description of cell behaviour when exposed to arrays of signals—biochemical, topographical and mechanical. Finally, with the aid of literature data, we attempt to draw unifying elements of the material–cytoskeleton–cell fate chain.

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“…Recent studies indicated that beyond the chemical specificity of the adhesive epitope, 2 many physical features of the adhesive surface, including its topography, 3 rigidity, 4 and precise epitope spacing, 5 are critical for guiding receptor-mediated adhesion formation and signalling. Specifically, it was demonstrated that cyclic RGDfK peptides linked to nanogold particles 6 which were arranged in pattern on substrates and interspaced by 58 or 73 nm, influence cell adhesion, 5 spreading, focal adhesion assembly, and migration 7,8 in very different ways. In these studies, control experiments demonstrated that only the specific functionalization of nanogold particles with cyclic RGD induced integrin clustering and such focal adhesion formation upon interaction with cells such as 3T3-fibroblasts or -* Corresponding author: spatz@mf.mpg.de.…”

Section: Introductionmentioning

confidence: 99%

Induction of Cell Polarization and Migration by a Gradient of Nanoscale Variations in Adhesive Ligand Spacing

et al. 2008

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Cell interactions with adhesive surfaces play a vital role in the regulation of cell proliferation, viability and differentiation, and affect multiple biological processes. Since cell adhesion depends mainly on the nature and density of the adhesive ligand molecules, spatial molecular patterning, which enables the modulation of adhesion receptor clustering, might affect both the structural and signalling activities of the adhesive interaction. We herein show that cells plated on surfaces that present a molecularly defined spacing gradient of an integrin RGD ligand, can sense small but consistent differences in adhesive ligand spacing of about 1 nm across the cell diameter, which is approximately 61 m when the spacing includes 70 nm. Consequently, these positional cues induce cell polarization, and initiate cell migration and signalling. We propose that differential positional clustering of the integrin transmembrane receptors is used by cells for exploring and interpreting their environment, at high spatial sensitivity.Adhesion of tissue cells to the extracellular matrix depends on the activation of specific transmembrane receptors; e.g. integrins, which leads to the assembly of specialized adhesion sites known as focal adhesions (FA). 1 Activation and spatial organization of integrins are mainly controlled by epitopes containing a RGD (R = arginine, G = glycine, D = aspartate) sequence, that are present on a variety of adhesive extracellular matrix (ECM) proteins. Recent studies indicated that beyond the chemical specificity of the adhesive epitope, 2 many physical features of the adhesive surface, including its topography, 3 rigidity, 4 and precise epitope spacing, 5 are critical for guiding receptor-mediated adhesion formation and signalling. Specifically, it was demonstrated that cyclic RGDfK peptides linked to nanogold particles 6 which were arranged in pattern on substrates and interspaced by 58 or 73 nm, influence cell adhesion, 5 spreading, focal adhesion assembly, and migration 7,8 in very different ways. In these studies, control experiments demonstrated that only the specific functionalization of nanogold particles with cyclic RGD induced integrin clustering and such focal adhesion formation upon interaction with cells such as 3T3-fibroblasts or -* Corresponding author: spatz@mf.mpg.de. + Both authors contributed equally to this work. 19 On the molecular length scale, these methods enable quantification of an average molecular concentration, which gradually varies along the adhesive surface; however, they are too "noisy" to quantify the densities themselves, and density variations capable of inducing cell polarization. NIH Public AccessWe herein demonstrate a novel surface patterning technique for the generation of nanoparticle spacing gradients, which is based on controlled modulation of the selfassembly of diblock copolymer micelles. Due to the self-assembly of macromolecules, large-scale surface areas are easily processed by this technique. After successful biofunctionalization of the nano...

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Lateral spacing of integrin ligands influences cell spreading and focal adhesion assembly

Cited by 342 publications

References 23 publications

Functional atlas of the integrin adhesome

Functional atlas of the integrin adhesome

Determinants of cell–material crosstalk at the interface: towards engineering of cell instructive materials

Induction of Cell Polarization and Migration by a Gradient of Nanoscale Variations in Adhesive Ligand Spacing

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