Nanoparticle-induced unfolding of fibrinogen promotes Mac-1 receptor activation and inflammation

Deng, Zhou J., Liang, Mingtao, Monteiro, Michael, Toth, Istvan and Minchin, Rodney F. (2011) Nanoparticle-induced unfolding of fibrinogen promotes Mac-1 receptor activation and inflammation. Nature Nanotechnology, 6 1: 39-44. doi:10.1038/NNANO.2010.250


Author Deng, Zhou J.
Liang, Mingtao
Monteiro, Michael
Toth, Istvan
Minchin, Rodney F.
Title Nanoparticle-induced unfolding of fibrinogen promotes Mac-1 receptor activation and inflammation
Journal name Nature Nanotechnology   Check publisher's open access policy
ISSN 1748-3387
1748-3395
Publication date 2011-01-01
Year available 2010
Sub-type Article (original research)
DOI 10.1038/NNANO.2010.250
Open Access Status Not yet assessed
Volume 6
Issue 1
Start page 39
End page 44
Total pages 6
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Language eng
Subject 1502 Bioengineering
3107 Atomic and Molecular Physics, and Optics
2204 Biomedical Engineering
2500 Materials Science
3104 Condensed Matter Physics
2208 Electrical and Electronic Engineering
Abstract The chemical composition, size, shape and surface characteristics of nanoparticles affect the way proteins bind to these particles, and this in turn influences the way in which nanoparticles interact with cells and tissues(1-5). Nanomaterials bound with proteins can result in physiological and pathological changes, including macrophage uptake(1,6), blood coagulation(7), protein aggregation(8) and complement activation(7,9), but the mechanisms that lead to these changes remain poorly understood. Here, we show that negatively charged poly(acrylic acid)conjugated gold nanoparticles bind to and induce unfolding of fibrinogen, which promotes interaction with the integrin receptor, Mac-1. Activation of this receptor increases the NF-kappa B signalling pathway, resulting in the release of inflammatory cytokines. However, not all nanoparticles that bind to fibrinogen demonstrated this effect. Our results show that the binding of certain nanoparticles to fibrinogen in plasma offers an alternative mechanism to the more commonly described role of oxidative stress in the inflammatory response to nanomaterials.
Formatted abstract
The chemical composition, size, shape and surface characteristics of nanoparticles affect the way proteins bind to these particles, and this in turn influences the way in which nanoparticles interact with cells and tissues. Nanomaterials bound with proteins can result in physiological and pathological changes, including macrophage uptake, blood coagulation, protein aggregation and complement activation, but the mechanisms that lead to these changes remain poorly understood. Here, we show that negatively charged poly(acrylic acid)-conjugated gold nanoparticles bind to and induce unfolding of fibrinogen, which promotes interaction with the integrin receptor, Mac-1. Activation of this receptor increases the NF-κB signalling pathway, resulting in the release of inflammatory cytokines. However, not all nanoparticles that bind to fibrinogen demonstrated this effect. Our results show that the binding of certain nanoparticles to fibrinogen in plasma offers an alternative mechanism to the more commonly described role of oxidative stress in the inflammatory response to nanomaterials.
© 2011 Macmillan Publishers Limited. All rights reserved.
Keyword In-vivo
Silica Nanoparticles
Gold nanoparticles
Protein adsorption
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID DP8787331
569694
Institutional Status UQ
Additional Notes Published online 19 December 2010. Published under Letters.

 
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Created: Sun, 30 Jan 2011, 10:02:15 EST