title: Modeling in vitro cellular responses to silver nanoparticles.
abstract: Engineered nanoparticles (NPs) have been widely demonstrated to induce toxic effects to various cell types. In vitro cell exposure systems have high potential for reliable, high throughput screening of nanoparticle toxicity, allowing focusing on particular pathways while excluding unwanted effects due to other cells or tissue dosimetry. The work presented here involves a detailed biologically based computational model of cellular interactions with NPs; it utilizes measurements performed in human cell culture systems in vitro, to develop a mechanistic mathematical model that can support analysis and prediction of in vivo effects of NPs. The model considers basic cellular mechanisms including proliferation, apoptosis, and production of cytokines in response to NPs. This new model is implemented for macrophages and parameterized using in vitro measurements of changes in cellular viability and mRNA levels of cytokines: TNF, IL-1b, IL-6, IL-8, and IL-10. The model includes in vitro cellular dosimetry due to nanoparticle transport and transformation. Furthermore, the model developed here optimizes the essential cellular parameters based on in vitro measurements, and provides a "stepping stone" for the development of more advanced in vivo models that will incorporate additional cellular and NP interactions.
authors.affiliation: Environmental and Occupational Health Sciences Institute (EOHSI), Rutgers University, Piscataway, NJ, USA ; Department of Environmental and Occupational Medicine, Robert Wood Johnson Medical School, Rutgers University, Piscataway, NJ, USA ; Department of Chemical and Biochemical Engineering, Rutgers University, Piscataway, NJ, USA.
authors.forename: Dwaipayan
authors.initials: D
authors.lastname: Mukherjee
authors.affiliation: Environmental and Occupational Health Sciences Institute (EOHSI), Rutgers University, Piscataway, NJ, USA ; Department of Environmental and Occupational Medicine, Robert Wood Johnson Medical School, Rutgers University, Piscataway, NJ, USA.
authors.forename: Steven G
authors.initials: SG
authors.lastname: Royce
authors.affiliation: Department of Environmental and Occupational Health, School of Public Health, Rutgers University, Piscataway, NJ, USA.
authors.forename: Srijata
authors.initials: S
authors.lastname: Sarkar
authors.affiliation: National Heart and Lung Institute, Imperial College London, London, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Thorley
authors.affiliation: Environmental and Occupational Health Sciences Institute (EOHSI), Rutgers University, Piscataway, NJ, USA ; Department of Environmental and Occupational Health, School of Public Health, Rutgers University, Piscataway, NJ, USA.
authors.forename: Stephan
authors.initials: S
authors.lastname: Schwander
authors.affiliation: Department of Materials and London Centre of Nanotechnology, Imperial College London, London, UK.
authors.forename: Mary P
authors.initials: MP
authors.lastname: Ryan
authors.affiliation: Department of Materials and London Centre of Nanotechnology, Imperial College London, London, UK.
authors.forename: Alexandra E
authors.initials: AE
authors.lastname: Porter
authors.affiliation: National Heart and Lung Institute, Imperial College London, London, UK.
authors.forename: Kian Fan
authors.initials: KF
authors.lastname: Chung
authors.affiliation: National Heart and Lung Institute, Imperial College London, London, UK.
authors.forename: Teresa D
authors.initials: TD
authors.lastname: Tetley
authors.affiliation: Nicholas School of Environment and Duke Global Health Institute, Duke University, Durham, NC, USA.
authors.forename: Junfeng
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Environmental and Occupational Health Sciences Institute (EOHSI), Rutgers University, Piscataway, NJ, USA ; Department of Environmental and Occupational Medicine, Robert Wood Johnson Medical School, Rutgers University, Piscataway, NJ, USA ; Department of Chemical and Biochemical Engineering, Rutgers University, Piscataway, NJ, USA.
authors.forename: Panos G
authors.initials: PG
authors.lastname: Georgopoulos