Elsevier

Analytical Biochemistry

Volume 505, 15 July 2016, Pages 8-17
Analytical Biochemistry

Binding kinetics and multi-bond: Finding correlations by synthesizing interactions between ligand-coated bionanoparticles and receptor surfaces

https://doi.org/10.1016/j.ab.2016.04.002Get rights and content

Abstract

The number of bonds formed between one single bionanoparticle and many surface receptors is an important subject to be studied but is seldom quantitatively investigated. A new evaluation of the correlation between binding kinetics and number of bonds is presented by varying ligand density and receptor density. An experimental system was developed using measurements with surface plasmon resonance spectroscopy. A corresponding multi-site adsorption model elucidated the correlation. The results show that with the increase of the receptor density, the adsorption rate first decreased when the number of bonds was below a maximum value and then increased when the number of bonds stayed at this maximum value. The investigation on ligand density variation suggests that the coating density on top of the bionanoparticle surface may have a particular value below which more ligand will accelerate the adsorption rate. The ratio of ligand amount bound by the receptors to the total ligand amount associated with a single bionanoparticle will remain constant even if one attaches more ligands to a bionanoparticle. We envision that the bionanoparticle desorption will not depend on density changes from either ligand or receptor when the number of bonds reaches a specific efficient value.

Section snippets

Materials

Polystyrene nanoparticles were purchased from Life Technologies, Thermo Fisher Scientific. Mes (2-(N-morpholino)ethanesulfonic acid monohydrate) was purchased from Carl Roth (Karlsruhe, Germany). Polyclonal human IgG, EDC (N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride), NHS (N-hydroxysuccinimide), glycine, and all other chemicals were purchased from Sigma–Aldrich. The dialysis membranes were purchased from Spectrum Labs (Frankfurt, Germany). Vivaspin 20 centrifugal concentrators

Results and discussion

In the current work, the ligand density was studied in the number of hundreds of ligands as opposed to previous studies [21], [28] focusing on tens of ligands per BioNP. Accordingly, the bonds formed by this BioNP with a high number of ligands also have the number in a range of hundreds. The multivalent interaction responds differently to density change of either the ligand or receptor. For example, Hartwell and coworkers showed that the signaling activity in immunotherapy depended on the

Conclusions

We have evaluated the multivalent effects in terms of the number of bonds formed between the ligands of single bionanoparticles and the surface receptors and demonstrated the correlation of the number of bonds with the binding kinetics by changing the densities of both ligand and receptor. For this purpose, an experimental system was first established where different types of BioNPs were synthesized by coating polystyrene nanoparticles with a variable amount of polyclonal human IgGs, and

Acknowledgment

W. Wang is affiliated with the International Max Planck Research School (IMPRS) for Advanced Methods in Process and System Engineering (Magdeburg) and gratefully acknowledges the scholarship from IMPRS.

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