Journal
ACS NANO
Volume 13, Issue 1, Pages 728-736Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsnano.8b08010
Keywords
multivalency; cooperativity; DNA nanotechnology; cancer cell; single molecule; biomimetic nanoarrays; spatial control
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Funding
- Chinese Scholarship Council
- BCI Cancer Research UK Centre Award
- Queen Mary University of London
- MRC [G0800825] Funding Source: UKRI
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We present a strategy for the fabrication of biomimetic nanoarrays, based on the use of DNA origami, that permits the multivalent investigation of ligand receptor molecule interactions in cancer cell spreading, with nanoscale spatial resolution and single-molecule control. We employed DNA origami to control the nanoscale spatial organization of integrin- and epidermal growth factor (EGF)-binding ligands that modulate epidermal cancer cell behavior. By organizing these multivalent DNA nanostructures in nanoarray configurations on nanopatterned surfaces, we demonstrated the cooperative behavior of integrin and EGF ligands in the spreading of human cutaneous melanoma cells: this cooperation was shown to depend on both the number and ratio of the selective ligands employed. Notably, the multivalent biochips we have developed allowed for this cooperative effect to be demonstrated with single-molecule control and nanoscale spatial resolution. By and large, the platform presented here is of general applicability for the study, with molecular control, of different multivalent interactions governing biological processes from the function of cell-surface receptors to protein ligand binding and pathogen inhibition.
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