Project #TER-5: Dynamic energy budget modeling of toxic effects of CdSe quantum dots
Roger M Nisbet , Tin Klanjscek, John Priester, Patricia Holden
Abstract:
The extraordinary pace of nanotechnology development has thus far exceeded society’s capacity to
predict, and thus mitigate against, unwanted effects on the environment. Similarly, the myriad of
biological receptors in the environment includes a nearly infinite number of organisms, life stages, and
biochemical pathways. Yet interactions of nanomaterials with biological receptors are inherently
anchored in biochemical bases that should be amenable to hypothesis formulation and testing using
mathematical modeling of fundamental interactions between nanomaterials and biological systems.
Quantitative structure activity relationships (QSARs) have great value in relating suborganismal
processes to organismal performance, but QSARs have limited transferability and utility for addressing
concerns about nanomaterials’ ecological effects – especially those involving populations and
ecosystems.
This research responds to the need for transferable models of nanomaterial effects on
ecological processes through the use of dynamic energy budget (DEB) modeling. DEB models use a
system of differential equations to represent energy acquisition and transduction processes in individual
organisms. Energy and elemental matter are the universal currencies of organismal growth,
reproduction, and induction of stress responses. DEB modeling characterizes the flow and
transformations of energy and key elements within organisms, making it possible to build models that
can relate individual function, population growth, and ultimately community composition and function.
We anticipate that DEB models will be powerful tools in predictive nanotoxicology, and aim to develop
and demonstrate their utility in this project. An immediate research product is new theory that uses
DEB models to characterize the response of individual organisms to exposure to nanomaterials and to
relate these responses to population and ecosystem level phenomena that are being studied in
experimental mesocosms.
We formulated DEB models appropriate for modeling bacterial responses to chemical stressors,
and are currently modifying the models as needed for testing against experiments that compared effects
of CdSe quantum dots versus soluble cadmium salts. We successfully developed a comprehensive DEB
modeling framework of cadmium effects on bacterial population growth and, with a limited number of
discrete and biologically-relevant parameters, demonstrated the excellent ability of DEB modeling to
represent experimentally-derived data. This is the first DEB model to invoke ROS as a mathematicallyrepresented damage inducing compound that impacts cell physiology and population dynamics. We also
evaluated the predictive power of the model , demonstrating that it can predict to good accuracy
bacterial growth for treatments of up to 150mg(Cd)/l using only parameters estimated from cadmium
treatments of 20mg(Cd)/l and lower. The model provides the foundation for future representations of
data from other studies involving different nanomaterials and organisms, and for predicting responses in
environments for which data are unavailable.
We extended our modeling to the CdSe quantum dot-bacterial interactions where published
experimental data by Holden and collaborators demonstrated that toxic effects of the nanoparticles
transcended those of cadmium ions above a concentration threshold. We collaborated with the Holden
group to design and conduct experiments to obtain the information necessary to calibrate data from
optical density (OD) measurements and to characterize dissolution of QDs. These experiments are
complete and the new data allowed generation of hypotheses to relate data to models and thereby help
identify the mechanisms that distinguish the response to QDs versus dissolved Cd.
We expect our research to not only impact the development of modeling approaches in
nanotoxicology but to also contribute to broader understanding the potential energetic basis for
nanoparticle-specific effects on organisms. Specifically, we are now developing a new, DEB-based
representation of ROS dynamics in cells that allows tracking of ROS generation, transformation, and
accumulation of the associated cellular damage.
This research also maps closely onto our work in projects MWF-3 and MWF-5, where DEB
modeling is being developed for describing and predicting toxicological effects of nanomaterials in
marine and freshwater ecosystems.