Mapping protein binding sites on the biomolecular corona of nanoparticles

Kelly, PM; Åberg, C; Polo, E; O'Connell, A; Cookman, J; Fallon, J; Krpetic, Z; Dawson, KA

Abstract

Nanoparticles in a biological milieu are known to form a sufficiently long-lived and well-organized ‘corona’ of biomolecules to confer a biological identity to the particle. Because this nanoparticle–biomolecule complex interacts with cells and biological barriers, potentially engaging with different biological pathways, it is important to clarify the presentation of functional biomolecular motifs at its interface. Here, we demonstrate that by using antibody-labelled gold nanoparticles, differential centrifugal sedimentation and various imaging techniques it is possible to identify the spatial location of proteins, their functional motifs and their binding sites. We show that for transferrin-coated polystyrene nanoparticles only a minority of adsorbed proteins exhibit functional motifs and the spatial organization appears random, which is consistent, overall, with a stochastic and irreversible adsorption process. Our methods are applicable to a wide array of nanoparticles and can offer a microscopic molecular description of the biological identity of nanoparticles.

• Journal Article Type: Article
• Acceptance Date: Feb 15, 2015
• Online Publication Date: Mar 30, 2015
• Publication Date: Mar 30, 2015
• Deposit Date: Oct 6, 2016
• Journal: Nature Nanotechnology
• Print ISSN: 1748-3387
• Electronic ISSN: 1748-3395
• Publisher: Nature Publishing Group
• Volume: 10
• Issue: 5
• Pages: 472-479
• DOI: https://doi.org/10.1038/nnano.2015.47
• Publisher URL: http://dx.doi.org/10.1038/nnano.2015.47
• Related Public URLs: http://www.nature.com/nnano/index.html
• Additional Information: Funders : Science Foundation Ireland (SFI);Irish Research Council;European Union Seventh Framework Programme; Projects : Principal Investigator Award;Embark scheme;NanoTransKinetics;NanoSolutions;NAMDIATREAM Nanotechnological Toolkit for Multi-modal Disease Diagnostics and Treatment Monitoring; Grant Number: 12/IA/1422; Grant Number: RS/2011/106; Grant Number: NMP4-2010-EU-US-266737; Grant Number: NMP-L6-2012-309329; Grant Number: NMP4-LA-2010- 246479