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Influence of ligand presentation density on the molecular recognition of mannose-functionalised glyconanoparticles by bacterial lectin BC2L-A

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Abstract

Polyvalent carbohydrate-protein interactions play a key role in bio- and pathological processes, including cell-cell communication and pathogen invasion. In order to study, control and manipulate these interactions gold nanoparticles have been employed as a 3D scaffold, presenting carbohydrate ligands in a multivalent fashion for use as high affinity binding partners and a model system for oligosaccharide presentation at biomacromolecular surfaces. In this study, the binding of a series of mannose-functionalised gold nanoparticles to the dimeric BC2L-A lectin from Burkholderia cenocepacia has been evaluated. BC2L-A is known to exhibit a high specificity for (oligo)mannosides. Due to the unique structure and binding nature of this lectin, it provides a useful tool to study (oligo)saccharides presented on multivalent scaffolds. Surface plasmon resonance and isothermal titration calorimetric assays were used to investigate the effect of ligand presentation density towards binding to the bacterial lectin. We show how a combination of structural complementarities between ligand presentation and lectin architecture and statistical re-binding effects are important for increasing the avidity of multivalent ligands for recognition by their protein receptors; further demonstrating the application of glyconanotechnology towards fundamental glycobiology research as well as a potential towards biomedical diagnostics and therapeutic treatments.

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Acknowledgments

The authors wish to thank the GlycoGold research training network, a part of the sixth research framework of the European Union, contract number MRTN-CT-2004-005645, for financial support. Financial support from the CNRS and ESRF are also acknowledged as well from the Labex Arcane (ANR-11-LABX-003) and the COST actions CM1102 and BM1003. We thank also the Spanish Ministry of Science and Innovation (MICINN, grant CTQ2011-27268) and the Department of Industry of the Basque Country (Etortek 2009). Dr Emilie Lameignere is greatly appreciated for help with lectin production. The SPR experiments were ran thanks to access to a Biacore T100 at the Plateforme Nanobio-Grenoble. SAXS experiments and analysis were carried out with the help of Drs Michael Sztucki and Emanuela Di Cola (ESRF, Grenoble). Professors Monica Palcic and Johannis Kamerling are also thanked for their helpful discussion.

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Authors and Affiliations

  1. Centre de Recherche sur les Macromolécules Végétales (CERMAV – CNRS), affiliated with Université Joseph Fourier Grenoble and ICMG, BP 53, 38041, Grenoble, France

    Michael Reynolds, Anne Imberty & Serge Pérez

  2. European Synchrotron Radiation Facility, 6 Rue Jules Horowitz, BP 220, 38043, Grenoble cedex 9, France

    Michael Reynolds

  3. Biofunctional Nanomaterials Unit, Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Po Miramón 182, 20009, San Sebastian, Spain

    Marco Marradi & Soledad Penadés

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  1. Michael Reynolds
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  2. Marco Marradi
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  5. Serge Pérez
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Correspondence to Serge Pérez.

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Reynolds, M., Marradi, M., Imberty, A. et al. Influence of ligand presentation density on the molecular recognition of mannose-functionalised glyconanoparticles by bacterial lectin BC2L-A. Glycoconj J 30, 747–757 (2013). https://doi.org/10.1007/s10719-013-9478-6

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