title: Nanoparticle-induced unfolding of fibrinogen promotes Mac-1 receptor activation and inflammation.
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.
authors.affiliation: School of Biomedical Sciences, University of Queensland, Brisbane 4072, Australia.
authors.forename: Zhou J
authors.initials: ZJ
authors.lastname: Deng
authors.forename: Mingtao
authors.initials: M
authors.lastname: Liang
authors.forename: Michael
authors.initials: M
authors.lastname: Monteiro
authors.forename: Istvan
authors.initials: I
authors.lastname: Toth
authors.forename: Rodney F
authors.initials: RF
authors.lastname: Minchin
mesh_terms: D000180:Acrylic Resins / Q000009:adverse effects; D001777:Blood Coagulation; D002460:Cell Line; D005340:Fibrinogen / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism*; D016177:Macrophage-1 Antigen / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry*; D018384:Oxidative Stress; D011485:Protein Binding; D058767:Protein Unfolding; D015398:Signal Transduction
chemical_list: D000180:Acrylic Resins; D016177:Macrophage-1 Antigen; D016328:NF-kappa B; C006903:carbopol 940; D005340:Fibrinogen