WP3

Multiscale modelling approaches

Objectives

To develop validated multiscale modelling approaches to identify how different patterns of release may influence physiological responses and how elements of MCNMs interact with each other, with other NMs and/or chemicals leading ultimately to mixture toxicity. To support with modelling the development of S&SbD strategies and the evaluation of their effectiveness.

Methodology

WP3 will develop an Open & FAIR database and will use all available data (e.g. from WP2) to identify the most relevant descriptors for prediction of the release, exposure, toxicokinetics, fate and hazard of MCNMs. Then, for advanced descriptors, WP3 will develop multiscale modelling approaches to evaluate the most common inter-component and nano-bio/eco interactions of MCNMs, also in mixtures with chemicals. Specifically, atomistic simulations will be performed to describe the MCNM structure and surface properties, such as hydration energy and interaction with building elements of biomolecules, and to parameterise mesoscopic models. The atomistic simulations will allow us to compute the Potentials of Mean Force (PMF) of MCNMs (components) systematically, which will be used in mesoscopic (coarse-grained) simulations to study nanoparticle release from MCNMs, aggregation kinetics of the MCNMs and their nanoparticle components in aqueous solution, and the conjugation with biomolecules (to model aggregation rates). Finally, continuum/mean field models will be used to evaluate integral properties of the materials and the medium, such as surface charge. Moreover, QSAR models will be developed to study the relationships between material properties and biological activity (toxicity), focusing on mixture toxicity. Those will be complemented by material flow and multimedia models of environmental distribution and fate, as well as models to study biodistribution and machine learning approaches to support the similarity assessment, grouping and read-across of MCNMs.

Key Outcomes

The SUNSHINE Open & FAIR database as well as modelling approaches for prediction of the unique properties and interactions of MCNMs, their release, biodistribution, fate and exposure and their toxicity (also in mixtures with chemicals). These models will be connected to the SIA e-infrastructure (WP1), also as part of the IATA, to underpin the development and validation of the S&SbD strategies (WP5).

Work Package Leader

CNRS