ModelingIn VitroCellular Responses to Silver Nanoparticles

Author:

Mukherjee Dwaipayan123,Royce Steven G.12,Sarkar Srijata4,Thorley Andrew5,Schwander Stephan14,Ryan Mary P.6,Porter Alexandra E.6,Chung Kian Fan5,Tetley Teresa D.5,Zhang Junfeng7,Georgopoulos Panos G.123

Affiliation:

1. Environmental and Occupational Health Sciences Institute (EOHSI), Rutgers University, Piscataway, NJ, USA

2. Department of Environmental and Occupational Medicine, Robert Wood Johnson Medical School, Rutgers University, Piscataway, NJ, USA

3. Department of Chemical and Biochemical Engineering, Rutgers University, Piscataway, NJ, USA

4. Department of Environmental and Occupational Health, School of Public Health, Rutgers University, Piscataway, NJ, USA

5. National Heart and Lung Institute, Imperial College London, London, UK

6. Department of Materials and London Centre of Nanotechnology, Imperial College London, London, UK

7. Nicholas School of Environment and Duke Global Health Institute, Duke University, Durham, NC, USA

Abstract

Engineered nanoparticles (NPs) have been widely demonstrated to induce toxic effects to various cell types.In vitrocell 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 systemsin vitro, to develop a mechanistic mathematical model that can support analysis and prediction ofin vivoeffects 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 usingin vitromeasurements of changes in cellular viability and mRNA levels of cytokines: TNF, IL-1b, IL-6, IL-8, and IL-10. The model includesin vitrocellular dosimetry due to nanoparticle transport and transformation. Furthermore, the model developed here optimizes the essential cellular parameters based onin vitromeasurements, and provides a “stepping stone” for the development of more advancedin vivomodels that will incorporate additional cellular and NP interactions.

Funder

National Institute of Environmental Health Sciences

Publisher

Hindawi Limited

Subject

Pharmacology,Toxicology

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