title: Molecular Dynamics of Fibrinogen Adsorption onto Graphene, but Not onto Poly(ethylene glycol) Surface, Increases Exposure of Recognition Sites That Trigger Immune Response.
abstract: Changes in the conformation of blood proteins due to their binding to nonbiological surfaces is the initial step in the chain of immunological reactions to foreign bodies. Despite the large number of experimental studies that have been performed on fibrinogen adsorption to nonbiological surfaces, a clear picture describing this complex process has eluded researchers to date. Developing a better understanding of the behavior of bioactive fibrinogen motifs upon their interaction with surfaces may facilitate the design of advanced materials with improved biocompatibility. This is especially important within the context of medical implants. Here we present results of explicit-solvent, all-atom MD simulations of the adsorption of the fibrinogen D-domain onto a graphene surface and a poly(ethylene glycol) (PEG) surface. Our results are consistent with experimental observations that interactions with PEG do not induce significant conformational changes on immune-reactive sites present in the D-domain of fibrinogen. In contrast, our results indicate that significant conformational changes induced by adsorption to graphene surfaces may occur under conditions that promote a high density of blood proteins on the surface. The structural rearrangements observed on graphene directly affect the secondary structure content of the D-domain, with consequent exposure of the recognition sites P1 (γ190-202) and P2 (γ377-395) and the subsite P2-C (γ383-395) involved in immune response. Analysis of the structural parameters of the MD conformers was shown to accurately assess the biocompatibility of the modeled surfaces.
authors.affiliation: Thunder Bay Regional Research Institute , 290 Munro Street, Thunder Bay, Ontario P7A 7T1, Canada.|Biotechnology Ph.D. Program, Faculty of Science and Environment Studies, Lakehead University , 955 Oliver Road, Thunder Bay, Ontario P7B 5E1, Canada.
authors.forename: Nadiya
authors.initials: N
authors.lastname: Dragneva
authors.affiliation: Thunder Bay Regional Research Institute , 290 Munro Street, Thunder Bay, Ontario P7A 7T1, Canada.|Department of Materials Science and Engineering, McMaster University , 1280 Main Street West, Hamilton, Ontario L8S 4L8, Canada.
authors.forename: Oleg
authors.initials: O
authors.lastname: Rubel
authors.affiliation: Thunder Bay Regional Research Institute , 290 Munro Street, Thunder Bay, Ontario P7A 7T1, Canada.|Biotechnology Ph.D. Program, Faculty of Science and Environment Studies, Lakehead University , 955 Oliver Road, Thunder Bay, Ontario P7B 5E1, Canada.|Department of Chemistry, Lakehead University , 955 Oliver Road, Thunder Bay, Ontario P7B 5E1, Canada.
authors.forename: Wely B
authors.initials: WB
authors.lastname: Floriano
mesh_terms: D000327:Adsorption; D000595:Amino Acid Sequence; D001665:Binding Sites; D001672:Biocompatible Materials / Q000737:chemistry; D005340:Fibrinogen / Q000737:chemistry* / Q000276:immunology*; D006108:Graphite / Q000737:chemistry*; D006801:Humans; D056004:Molecular Dynamics Simulation; D011092:Polyethylene Glycols / Q000737:chemistry*; D017433:Protein Structure, Secondary; D012997:Solvents / Q000737:chemistry; D013499:Surface Properties; D013816:Thermodynamics
chemical_list: D001672:Biocompatible Materials; D012997:Solvents; D011092:Polyethylene Glycols; D006108:Graphite; D005340:Fibrinogen