Impact of Local versus Global Ligand Density on Cellular Adhesion

Deeg, Janosch; Louban, Ilia; Aydin, Daniel; Selhuber‐Unkel, Christine; Kessler, Horst; Spatz, Joachim P.

doi:10.1021/nl104079r

Cited by 148 publications

(189 citation statements)

References 40 publications

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“…Ligand density influences cell adhesion strength and focal adhesion formation. [40][41][42] In light of this observation, we infer that the deflection of SiNWs brings adjacent SiNWs in close proximity, thus facilitating the formation of focal adhesion complexes.…”

Section: Resultsmentioning

confidence: 87%

Deflection induced cellular focal adhesion and anisotropic growth on vertically aligned silicon nanowires with differing elasticity

et al. 2016

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Cellular adhesion and growth on substrates with differing surface topography are known to induce unusual cell behaviors. Here, we investigated the adhesion and growth of human embryonic kidney 293T cells on vertically aligned silicon nanowires. Varying the diameter of nanowires affected their elasticity, which in turn caused variations in cell morphology and adhesion. Calculation of their elastic modulus revealed that long and thin nanowires are easier to deflect and thus provide more focal adhesion sites for adherent cells. And, induced mechanical tension triggered cellular anisotropic growth in the direction of tension, creating a greater rate of filopodium growth than was observed with a bare glass substrate devoid of mechanical tension. This nanotopographical approach provides important insights into the role of artificial substrates in the modulation of cell behavior and a conceptual framework for further analysis of substrate-induced changes in cellular activity.

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Section: Resultsmentioning

confidence: 87%

Deflection induced cellular focal adhesion and anisotropic growth on vertically aligned silicon nanowires with differing elasticity

et al. 2016

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“…These studies indicated that integrin binding and clustering, the consequent assembly of FAs and cell spreading are strongly influenced by fine changes in adhesive cues. It has been proposed that inter-ligand spacing ranging from 58 to 73 nm is required for successful integrin-mediated signaling activation [15,16], and that local, more than global ligand distribution seems to be a key surface parameter for the assembly and stability of FA complexes [18][19][20]. At the nanoscale, the number and geometric distribution of receptors, as well as their binding strengths, exert a profound effect on cell adhesion strength, by means of a cooperative integrin clustering mechanism [20][21][22].…”

Section: Introductionmentioning

confidence: 99%

“…It has been proposed that inter-ligand spacing ranging from 58 to 73 nm is required for successful integrin-mediated signaling activation [15,16], and that local, more than global ligand distribution seems to be a key surface parameter for the assembly and stability of FA complexes [18][19][20]. At the nanoscale, the number and geometric distribution of receptors, as well as their binding strengths, exert a profound effect on cell adhesion strength, by means of a cooperative integrin clustering mechanism [20][21][22]. Although the physiological relevance of ligand spacing regulation is still unclear, these findings clearly expose the exquisite cellular sensing machinery, thus providing a sound approach for further eliciting and unraveling specific cellular responses to their environment.…”

Section: Introductionmentioning

confidence: 99%

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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“…71 Micro-and nanopatterned surfaces functionalized with integrin ligands have been used to investigated integrin-based adhesion of fibroblasts. 72 This study revealed that the spatial organization of ligands plays a crucial role in cellular adhesion, with local, rather than global, ligand density promoting focal adhesion formation. This dependency on the interligand spacing is critical for designing biocompatible biomedical implants.…”

Section: Effect Of Surface Chemistrymentioning

confidence: 86%

Elucidating the molecular mechanisms underlying cellular response to biophysical cues using synthetic biology approaches

Denning

Roos

2016

Cell Adhesion & Migration

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The use of synthetic surfaces and materials to influence and study cell behavior has vastly progressed our understanding of the underlying molecular mechanisms involved in cellular response to physicochemical and biophysical cues. Reconstituting cytoskeletal proteins and interfacing them with a defined microenvironment has also garnered deep insight into the engineering mechanisms existing within the cell. This review presents recent experimental findings on the influence of several parameters of the extracellular environment on cell behavior and fate, such as substrate topography, stiffness, chemistry and charge. In addition, the use of synthetic environments to measure physical properties of the reconstituted cytoskeleton and their interaction with intracellular proteins such as molecular motors is discussed, which is relevant for understanding cell migration, division and structural integrity, as well as intracellular transport. Insight is provided regarding the next steps to be taken in this interdisciplinary field, in order to achieve the global aim of artificially directing cellular response.

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Impact of Local versus Global Ligand Density on Cellular Adhesion

Cited by 148 publications

References 40 publications

Deflection induced cellular focal adhesion and anisotropic growth on vertically aligned silicon nanowires with differing elasticity

Deflection induced cellular focal adhesion and anisotropic growth on vertically aligned silicon nanowires with differing elasticity

Focal adhesion stabilization by enhanced integrin-cRGD binding affinity

Elucidating the molecular mechanisms underlying cellular response to biophysical cues using synthetic biology approaches

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