Integrated Cell Response Measures
PNNL researchers are developing a computational modeling framework that bridges nanoparticle dosimetry (exposure) and cell response pathways, forming the basis for an integrated and predictive approach to assess biological response to nanoparticle exposure.
Experimental tools and computational approaches help us understand the role that specific cell surface receptors play in mediating the initial interactions between nanomaterials and cells, and to determine the relationships between surface properties of the nanomaterials and cellular uptake, and subsequent biological response. As an example, the model below is used to conceptualize the response of macrophages or scavenger receptors and epithelial cells to nanomaterials, the focus of some of our recent research.
In parallel to our experimental activities described in other multiple sections of this website, we are developing statistically-based quantitative structure-activity relationship (QSAR) models that can be used to identify quantitative and predictive relationships between the properties of chemicals and their biological effects. The QSAR models will include molecular level descriptors of the particle surface physical and chemical properties of the nanomaterials with the ultimate goal of determining specific properties that dictate cell uptake and the relationships between cell uptake and cellular responses. These QSAR models will allow us to couple the kinetic data describing receptor mediated nanoparticle uptake with multiple protein secretion profiles of macrophage activation, and provide a mathematical description of the key nanomaterial properties that drive these events.
Contact: Brian Thrall