Research Capabilities
Modeling Nanoparticle-Cell Interactions
This project will develop a framework linking computational dosimetry of nanomaterials with cell response (pathway and network) analysis.
Research on environmental biomarkers at PNNL has focused on integrated genomic, proteomic and imaging technologies needed to develop biosignatures of cellular response to engineered nanoparticles. The compendium of data resulting from these efforts is providing new information and biomarkers of specific pathways stimulated by nanomaterial exposure. In parallel, computational models describing the delivery of nanoparticles to cells in vitro and in the lung are being developed and experimentally verified. However, precise mechanisms and pathways for internalization have yet to be established. This project will develop a modeling framework which bridges nanoparticle dosimetry (exposure) and cell response pathways, forming the basis for an integrated and predictive approach for assessing biological responses to nanoparticles. We propose to develop computational models which describe the initial and key interactions of nanoparticles with cells which govern their cellular uptake. We hypothesize that the internalization of nanoparticles and subsequent cellular responses are at least in part receptor-mediated, and are thereby influenced by the level of receptor expression and by particle surface chemistry. Thus, our focus will be to develop quantitative kinetic models of nanoparticle internalization in macrophages, and to use these models to evaluate the relationships between external cell dose, nanoparticle surface chemistry, and cellular response.