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Abstract
Glycan-lectin interactions drive a diverse range of biological signaling and recognition processes. The display of glycans in multivalent format enables their intrinsically weak binding affinity to lectins to be overcome by the cluster glycoside effect, which results in a non-linear increase in binding affinity. As many lectins have multiple binding sites, upon interaction with glycosylated nanomaterials either aggregation or surface binding without aggregation can occur. Depending on the application area, either one of these responses are desirable (or undesirable) but methods to tune the aggregation state, independently from the overall extent/affinity of binding are currently missing. Herein, we use gold nanoparticles decorated with galactose-terminated polymer ligands, obtained by photo-initiated RAFT polymerization to ensure high end-group fidelity, to show the dramatic impact on agglutination behaviour due to the chemistry of the polymer linker. Poly(N-hydroxyethyl acrylamide) (PHEA)-coated gold nanoparticles, a polymer widely used as a non-ionic stabilizer, showed preference for aggregation with lectins compared to poly(N-(2-hydroxypropyl)methacrylamide) (PHPMA)-coated nanoparticles which retained colloidal stability, across a wide range of polymer lengths and particle core sizes. Using biolayer interferometry, it was observed that both coatings gave rise to similar binding affinity and hence provided conclusive evidence that aggregation rate alone cannot be used to measure affinity between nanoparticle systems with different stabilizing linkers. This is significant, as turbidimetry is widely used to demonstrate glycomaterial activity, although this work shows the most aggregating may not be the most avid, when comparing different polymer backbones/coating. Overall, our findings underline the potential of PHPMA as the coating of choice for applications where aggregation upon lectin binding would be problematic, such as in vivo imaging or drug delivery.
Highlights
Glycan–lectin interactions drive a diverse range of biological signaling and recognition processes
Poly(N-hydroxyethyl acrylamide) (PHEA)-coated gold nanoparticles, a polymer widely used as a non-ionic stabilizer, showed preference for aggregation with lectins compared to poly(N-(2-hydroxypropyl)methacrylamide) (PHPMA)-coated nanoparticles which retained colloidal stability, across a wide range of polymer lengths and particle core sizes
Rather than traditional thermal reversible addition–fragmentation chain transfer (RAFT) polymerization, photo-RAFT was chosen as it removes the need for heating, it is extremely convenient to undertake in the laboratory and as no external radical source is used, end-group fidelity is maximized.[63,64]
Summary
Glycomaterials are emerging as tools to modulate complex cellular function: Godula and co-workers remodelled neural progenitor cells with sulphated glycans to control their differentiation,[14] mannosylated nanoparticles can potentiate vaccines[15] and glycosylated nanomaterials have been used to aid cellular delivery.[16,17,18,19,20] For instance, glucose- and galactosecoated iron oxide nanoparticles have been prepared and the influence of the glycan versus poly(ethylene glycol)-coating on the cellular uptake by several cell lines has been studied.[17]. Field and co-workers used short PEG linkers to install sialic acids onto AuNPs for the discrimination between avian and human influenza.[39] Gibson and co-workers have exploited reversible addition–fragmentation chain transfer (RAFT) polymerization to generate stabilizing poly(N-hydroxyethyl acrylamide) (PHEA) ligands for AuNPs: RAFT installs sulfur containing endgroups which have high affinity for gold surfaces.[41,42,43] By using RAFT agents, with a pentafluorophenyl ester end-group, aminoglycans can be attached The advantage of this controlled radical polymerization[44] method is that the length of the linker can be tuned to achieve the delicate balance between stability (favored by longer chain length polymers) and aggregationresponse (favored by shorter chain lengths).[45,46,47,48] This strategy is highly tunable, and has been used to probe the binding of a range of lectins, and to probe carbohydrate–carbohydrate interactions.[49]. A detailed X-ray photoelectron spectroscopy (XPS) study indicated that intrinsic grafting density differences contribute to this tuneable behaviour, influenced by the chemistry of the linker
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