The effect of ligand affinity on integrins’ lateral diffusion in cultured cells

Mainali, Dipak; Smith, Emily A.

doi:10.1007/s00249-012-0873-x

Cited by 13 publications

(13 citation statements)

References 48 publications

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“…Thus, the talin-GFP exchange rate is increased in Parvin mutants; however, the mys b58 GOF allele is sufficient to restore it. Single-particle tracking studies using the mys b58 (V409D) mutation in S2 cells further support our findings (Mainali and Smith, 2013). In accordance with recent studies on mammalian ILK (Huet-Calderwood et al, 2014;Ye et al, 2013), we cannot exclude the possibility that the reduced integrin immobile fraction at the PM compromises the sustainability of integrin clustering (Welf et al, 2012).…”

Section: Discussionsupporting

confidence: 91%

IPP Complex Reinforces Adhesion by Relaying Tension-Dependent Signals to Inhibit Integrin Turnover

et al. 2016

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Cytoskeleton-mediated forces regulate the assembly and function of integrin adhesions; however, the underlying mechanisms remain unclear. The tripartite IPP complex, comprising ILK, Parvin, and PINCH, mediates the integrin-actin link at Drosophila embryo muscle attachment sites (MASs). Here, we demonstrate a developmentally earlier function for the IPP complex: to reinforce integrin-extracellular matrix (ECM) adhesion in response to tension. In IPP-complex mutants, the integrin-ECM linkage at MASs breaks in response to intense muscle contractility. Mechanistically, the IPP complex is required to relay force-elicited signals that decelerate integrin turnover at the plasma membrane so that the integrin immobile fraction is adequate to withstand tension. Epistasis analysis shows that alleviation of muscle contractility, downregulation of endocytosis, and enhanced integrin binding to the ECM are sufficient to restore integrin-ECM adhesion and maintain integrin-adhesome organization in IPP-complex mutants. Our findings reveal a role for the IPP complex as an essential mechanosensitive regulatory switch of integrin turnover in vivo.

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Section: Discussionsupporting

confidence: 91%

IPP Complex Reinforces Adhesion by Relaying Tension-Dependent Signals to Inhibit Integrin Turnover

et al. 2016

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“…contribute to the signal [67][68][69]. Furthermore, it could be that the great heterogeneity in lateral mobility could be associated with the experimental conditions.…”

Section: Resultsmentioning

confidence: 99%

“…The results obtained for fibroblasts on nanopatterns functionalized with the polyproline-based ligand enable us to infer that β3 integrins display a slower rate of integrin-ligand dissociation, implying longer residence at FAs. A slower diffusion rate can also be associated with higher integrin-ligand affinity [68,70,71]. Several studies have shown that increasing the affinity between integrins and the binding domain restricts lateral diffusion.…”

Section: Resultsmentioning

confidence: 99%

“…It was recently reported that activation of the highaffinity integrin receptor lymphocyte function-associated antigen 1 (LFA-1) by extracellular Ca 2 + depletion resulted in reduction of the TS2/4-ATTO520-labeled LFA-1 mobile fraction [71]. In another study, a comparison of lateral diffusion rates between the WT αPS2CβPS and the highaffinity mutant αPS2CβPS409D was made by single-particle tracking, resulting in a decreased mobile fraction and a slower diffusion coefficient for the mutant integrin [68]. These experiments, together with the previous cell adhesion and biochemical experiments, clearly prove that small changes in adhesive chemical cues have a strong influence on the cell adhesion process.…”

Section: Resultsmentioning

confidence: 99%

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Focal adhesion stabilization by enhanced integrin-cRGD binding affinity

et al. 2017

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Abstract:In this study we investigate the impact of ligand presentation by various molecular spacers on integrin-based focal adhesion formation. Gold nanoparticles (AuNPs) arranged in hexagonal patterns were biofunctionalized with the same ligand head group, cyclic Arg-Gly-Asp [c(-RGDfX-)], but with different molecular spacers, each of which couples the head group to the gold. Aminohexanoic acid, polyethylene glycol (PEG) and polyproline spacers were used to vary the distance between the binding motif and the substrate, and thus the presentation of integrin binding on anchoring points. Adherent cells plated on nanopatterned surfaces with polyproline spacers for peptide immobilization could tolerate larger ligand spacing (162 nm) for focal adhesion formation, in comparison to cells on surfaces with PEG (110 nm) or aminohexanoic acid (62 nm) spacers. Due to the rigidity of the polyproline spacer, enhanced access to the ligand-binding site upon integrin-cRGD complex formation increases the probability of rebinding and decreases unbinding, as measured by fluorescence recovery after photobleaching (FRAP) analysis, compared to the analogues with aminohexanoic acid or PEGcontaining spacers. These findings indicate that focal adhesion formation may not only be stabilized upon tight integrin clustering, but also by tuning the efficiency of the exposure of the cRGD-based ligand to the integrin extracellular domains. Our studies clearly highlight the importance of ligand spatial presentation for regulating adhesion-dependent cell behavior, and provide a sound approach for studying cell signaling processes on nanometer-scale, engineered bioactive surfaces under chemical stimuli of varying intensities.

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“…No significant differences were observed between the Ahx-and the PEG-based ligands, although this discrepancy could be interpreted by considering each pool of integrin measured in the experiment. In FRAP, all integrins, whether bound to the ligand or not, are fluorescently labeled, and within the membrane region probed, contribute to the signal [67], [68], [69]. Furthermore, it could be that the great heterogeneity in lateral mobility could be associated with the experimental conditions.…”

Section: Peptide Descriptionmentioning

confidence: 99%

Focal adhesion stabilization by enhanced integrin-cRGD binding affinity

Pallarola¹,

Platzman²,

Bochen³

et al. 2018

Nano Online

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In this study we investigate the impact of ligand presentation by various molecular spacers on integrin-based focal adhesion formation. Gold nanoparticles (AuNPs) arranged in hexagonal patterns were biofunctionalized with the same ligand head group, cyclic Arg-Gly-Asp [c(-RGDfX-)], but with different molecular spacers, each of which couples the head group to the gold. Aminohexanoic acid, polyethylene glycol (PEG) and polyproline spacers were used to vary the distance between the binding motif and the substrate, and thus the presentation of integrin binding on anchoring points. Adherent cells plated on nanopatterned surfaces with polyproline spacers for peptide immobilization could tolerate larger ligand spacing (162 nm) for focal adhesion formation, in comparison to cells on surfaces with PEG (110 nm) or aminohexanoic acid (62 nm) spacers. Due to the rigidity of the polyproline spacer, enhanced access to the ligand-binding site upon integrin-cRGD complex formation increases the probability of rebinding and decreases unbinding, as measured by fluorescence recovery after photobleaching (FRAP) analysis, compared to the analogues with aminohexanoic acid or PEG-containing spacers. These findings indicate that focal adhesion formation may not only be stabilized upon tight integrin clustering, but also by tuning the efficiency of the exposure of the cRGD-based ligand to the integrin extracellular domains. Our studies clearly highlight the importance of ligand spatial presentation for regulating adhesion-dependent cell behavior, and provide a sound approach for studying cell signaling processes on nanometer-scale, engineered bioactive surfaces under chemical stimuli of varying intensities.

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The effect of ligand affinity on integrins’ lateral diffusion in cultured cells

Cited by 13 publications

References 48 publications

IPP Complex Reinforces Adhesion by Relaying Tension-Dependent Signals to Inhibit Integrin Turnover

IPP Complex Reinforces Adhesion by Relaying Tension-Dependent Signals to Inhibit Integrin Turnover

Focal adhesion stabilization by enhanced integrin-cRGD binding affinity

Focal adhesion stabilization by enhanced integrin-cRGD binding affinity

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