journal article·2015-05Open access

Mapping protein binding sites on the biomolecular corona of nanoparticles

Philip M. Kelly, Christoffer Åberg, Ester Polo, Ann O'Connell, Jennifer Cookman, Jonathan Fallon, Željka Krpetić, Kenneth A. Dawson

Nature Nanotechnology· Volume 10· Issue 5

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.
Source: europepmc · Quality: candidate unverified · Source record ↗

Research context

OpenAlex topics: Nanoparticle-Based Drug Delivery · Polymer Surface Interaction Studies · Nanoparticles: synthesis and applications

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

References (31)

Show source-provided references
1. Monopoli, M. P., Åberg, C., Salvati, A. & Dawson, K. A. Biomolecular coronas provide the biological identity of nanosized materials. Nature Nanotech. 7, 779–786 (2012).10.1038/nnano.2012.207 ↗
2. Cedervall, T. et al. Understanding the nanoparticle–protein corona using methods to quantify exchange rates and affinities of proteins for nanoparticles. Proc. Natl Acad. Sci. USA 104, 2050–2055 (2007).10.1073/pnas.0608582104 ↗
3. Nel, A. E. et al. Understanding biophysicochemical interactions at the nano–bio interface. Nature Mater. 8, 543–557 (2009).10.1038/nmat2442 ↗
4. Tenzer, S. et al. Rapid formation of plasma protein corona critically affects nanoparticle pathophysiology. Nature Nanotech. 8, 772–781 (2013).10.1038/nnano.2013.181 ↗
5. Hellstrand, E. et al. Complete high-density lipoproteins in nanoparticle corona. FEBS J. 276, 3372–3381 (2009).10.1111/j.1742-4658.2009.07062.x ↗
6. Wan, S. et al. The ‘sweet’ side of the protein corona: effects of glycosylation on nanoparticle–cell interactions. ACS Nano 9, 2157–2166 (2015).10.1021/nn506060q ↗
7. Casals, E., Pfaller, T., Duschl, A., Oostingh, G. J. & Puntes, V. Time evolution of the nanoparticle protein corona. ACS Nano 4, 3623–3632 (2010).10.1021/nn901372t ↗
8. Maiorano, G. et al. Effects of cell culture media on the dynamic formation of protein–nanoparticle complexes and influence on the cellular response. ACS Nano 4, 7481–7491 (2010).10.1021/nn101557e ↗
9. Walkey, C. D. & Chan, W. C. W. Understanding and controlling the interaction of nanomaterials with proteins in a physiological environment. Chem. Soc. Rev. 41, 2780–2799 (2012).10.1039/C1CS15233E ↗
10. Walczyk, D., Baldelli Bombelli, F., Monopoli, M. P., Lynch, I. & Dawson, K. A. What the cell ‘sees’ in bionanoscience. J. Am. Chem. Soc. 132, 5761–5768 (2010).10.1021/ja910675v ↗
11. Fleischer, C. & Payne, C. K. Secondary structure of corona proteins determines the cell surface receptors used by nanoparticles. J. Phys. Chem. B 118, 14017–14026 (2014).10.1021/jp502624n ↗
12. Treuel, L. et al. Impact of protein modification on the protein corona on nanoparticles and nanoparticle–cell interactions. ACS Nano 8, 503–513 (2014).10.1021/nn405019v ↗
13. Zensi, A. et al. Albumin nanoparticles targeted with Apo E enter the CNS by transcytosis and are delivered to neurones. J. Control. Release 137, 78–86 (2009).10.1016/j.jconrel.2009.03.002 ↗
14. Deng, Z. J., Liang, M., Monteiro, M., Toth, I. & Minchin, R. F. Nanoparticle-induced unfolding of fibrinogen promotes Mac-1 receptor activation and inflammation. Nature Nanotech. 6, 39–44 (2011).10.1038/nnano.2010.250 ↗
15. Jiang, X. et al. Quantitative analysis of the protein corona on FePt nanoparticles formed by transferrin binding. J. R. Soc. Interface 7, S5–S13 (2010).
16. Martel, J. et al. Comprehensive proteomic analysis of mineral nanoparticles derived from human body fluids and analyzed by liquid chromatography–tandem mass spectrometry. Anal. Biochem. 418, 111–125 (2011).10.1016/j.ab.2011.06.018 ↗
17. Sund, J., Alenius, H., Vippola, M., Savolainen, K. & Puustinen, A. Proteomic characterization of engineered nanomaterial–protein interactions in relation to surface reactivity. ACS Nano 5, 4300–4309 (2011).10.1021/nn101492k ↗
18. Mortimer, G. M. et al. Cryptic epitopes of albumin determine mononuclear phagocyte system clearance of nanomaterials. ACS Nano 8, 3357–3366 (2014).10.1021/nn405830g ↗
19. Milani, S., Baldelli Bombelli, F., Pitek, A. S., Dawson, K. A. & Rädler, J. Reversible versus irreversible binding of transferrin to polystyrene nanoparticles: soft and hard corona. ACS Nano 6, 2532–2541 (2012).10.1021/nn204951s ↗
20. Pitek, A. S. et al. Transferrin coated nanoparticles: study of the bio–nano interface in human plasma. PLoS ONE 7, e40685 (2012).10.1371/journal.pone.0040685 ↗
21. Slot, J. W. & Geuze, H. J. A new method of preparing gold probes for multiple-labeling cytochemistry. Eur. J. Cell Biol. 38, 87–93 (1985).
22. Hancock, J. F. & Prior, I. A. Electron microscopic imaging of Ras signaling domains. Methods 37, 165–172 (2005).10.1016/j.ymeth.2005.05.018 ↗
23. Cheng, Y., Zak, O., Aisen, P., Harrison, S. C. & Walz, T. Structure of the human transferrin receptor–transferrin complex. Cell 116, 565–576 (2004).10.1016/S0092-8674(04)00130-8 ↗
24. Mason, A. B. et al. A loop in the N-lobe of human serum transferrin is critical for binding to the transferrin receptor as revealed by mutagenesis, isothermal titration calorimetry, and epitope mapping. J. Mol. Recogn. 22, 521–529 (2009).10.1002/jmr.979 ↗
25. Carney, R. P. et al. Determination of nanoparticle size distribution together with density or molecular weight by 2D analytical ultracentrifugation. Nature Commun. 2, 335 (2011).10.1038/ncomms1338 ↗
26. Wang, J., Tian, S., Petros, R. A., Napier, M. E. & DeSimone, J. M. The complex role of multivalency in nanoparticles targeting the transferrin receptor for cancer therapies. J. Am. Chem. Soc. 132, 11306–11313 (2010).10.1021/ja1043177 ↗
27. Hansen, J. P. & McDonald, I. R. Theory of Simple Liquids 3rd edn (Academic Press, 2006).
28. Dawson, K. A. The glass paradigm for colloidal glasses, gels, and other arrested states driven by attractive interactions. Curr. Opin. Colloid Interface Sci. 7, 218–227 (2002).10.1016/S1359-0294(02)00052-3 ↗
29. Salvati, A. et al. Transferrin-functionalized nanoparticles lose their targeting capabilities when a biomolecule corona adsorbs on the surface. Nature Nanotech. 8, 137–143 (2013).10.1038/nnano.2012.237 ↗
30. Berman, H. M. et al. The protein data bank. Nucleic Acids Res. 28, 235–242 (2000).10.1093/nar/28.1.235 ↗
31. Pettersen, E. F. et al. UCSF chimera—a visualization system for exploratory research and analysis. J. Comput. Chem. 25, 1605–1612 (2004).10.1002/jcc.20084 ↗