INSPIRE Track1: Computational Design for the Safe Development of High-Aspect-Ration Nanomaterials

Brown University, Providence RI

Investigators

Abstract

Abstract CBET - 1344097 Hurt, Robert H. This INSPIRE award is partially funded by the Nano EHS Program and the Particulate and Multiphase Processes Program in the Chemical Biomedical Environmental and Transport Division in the Directorate for Engineering and the Nano & Bio Mechanics Program and the Mechanics of Materials Program in the Civil, Mechanical and Manufacturing Innovation Division of the Engineering Directorate. This proposed Track 1 INSPIRE project seeks to identify fundamental design rules to allow the safe development of high-aspect ratio nanomaterials (HARNs). HARNs are a class of one-dimensional fiber-like or two-dimensional sheet-like materials that include carbon nanotubes, metal nanowires, and graphene. Simple isometric nanoparticles often initiate toxicity pathways through chemical surface processes that include redox reactions and release of soluble toxicants. There is increasing evidence that HARNs depart from this paradigm by initiating toxicity pathways through geometric and nanomechanical interactions with target cells. Exposure to long, nano-thin fibers or atomically thin sheets of large lateral dimension can impair internalization and intracellular sequestration mechanisms leading to frustrated uptake, membrane damage, lysosomal permeabilization, and toxicity. Each of these steps involves the interaction of a complex material shape with a biological membrane that surrounds the cell or defines a vesicle within the cell. Key to the safe design of HARNs is to understand how geometry determines these biomechanical interactions. This INSPIRE project is a joint effort of two NSF programs: CBET Environmental Health and Safety of Nanotechnology (lead), and CMMI Biomechanics and Mechanobiology. Intellectual Merit : The project team hypothesizes that the biological response to HARNs is mediated by geometric parameters, namely length and stiffness for carbon nanotubes and lateral dimension and stiffness for graphene-family nanomaterials. A systematic study of the geometric and mechanical interactions of HARNs with biological membranes and target cells is proposed using a combination of molecular dynamics simulations and biological experimental validation on a set of carefully engineered materials of varying length and lateral dimension. Course-grained and all-atom molecular dynamics simulations and supporting analytical methods will be used to model lipid bilayers interacting with HARNs of defined geometries to understand uptake mechanisms, vesicular packaging and trafficking, lysosomal damage, and cytotoxicity. Parallel experimental validation will expose lung epithelial cells and fish gill cells to a unique panel of HARNs that include multi-walled carbon nanotubes cut to well-defined lengths, and few-layer graphene materials of varying lateral dimension. The close integration of modeling and experiment has the potential to achieve breakthroughs in our basic understanding of the structure-activity relations that determine nanotoxicity for these emerging nanoproducts. Broader Impacts: The development of new nanotechnologies should be accompanied by parallel efforts to understand and manage their risks to human health and the environment. Two of the most important materials in the nanosafety field today are carbon nanotubes and graphene, both of which are emerging as high-production-volume products with a high priority for hazard assessment. The basic scientific work we propose has the potential to identify the geometric features of HARNs that are the underlying cause of adverse health outcomes, and allow industry to re-design or re-formulate the materials to avoid those features for improved consumer and worker safety. This project will also cross-train a diverse group of Ph.D. students, post-doctoral researchers and undergraduates at the interface of materials science, molecular modeling, and toxicology, and prepare them for careers in nanotechnology research or industry. Finally the investigators will engage in public policy discussions in the area of nanotechnology business, safety and regulation, and will help translate scientific findings relevant to the emerging nanotube and graphene business sectors. The investigators will continue to engage in national discussions on the potential for "prevention by design" at agencies and agency-sponsored workshops that involve business, legal, and regulatory professionals.