Project 2: Adverse Human Health Impacts of Nanomaterials

Significance

Graphene-family nanomaterials (GFNs) including monolayer graphene, few-layer graphene, ultrathin graphite, and graphene oxide are new engineered carbon nanomaterials. These materials can be manufactured at large scale by thermal or mechanical exfoliation generating respirable dry powders; however, potential toxicity following inhalation into the lungs is unknown. Project 2, in collaboration with Project 4, will develop graphene-based environmental barriers in a responsible manner that considers both performance and potential adverse human health impacts throughout the design and evaluation phases.

Overview

Graphene is an emerging engineered nanomaterial entering large-scale commercial development. It is the first member of a rapidly expanding family of atomically thin, 2D layered materials or sheets that are predicted to play a major role in the nanotechnology industry in the 21st century for new electronic and magnetic materials, layered semiconductors, catalysts, biosensors, and biomedical applications. Widespread commercialization and biological applications will lead to interactions with cellular and biological structures with potential adverse environmental and health impacts. The relationships between the unique chemical, electronic, and mechanical properties of atomically thin 2D sheets and potential toxicity are unknown. This interdisciplinary collaboration between Robert Hurt (Project 4), and Agnes Kane (Project 2) will investigate the fundamental nanomechanical interactions of atomically thin, 2D nanomaterials with target cells in lungs.

This interdisciplinary research team has successfully used coarse-grained molecular dynamics, all-atom steered molecular dynamics, analytical modeling, and ex situ bioimaging to investigate penetration of plate-like graphene microsheets into biological lipid bilayers (Li et al., PNAS USA, 2013). As illustrated in Figure 1, ex situ scanning electron microscopy validated the predicted mode of penetration of grapheneMacrophages_Graphene-Interaction_project2Macrophages_Graphene-Interaction_project2 microsheets at sharp corners or edges into a cellular membrane based on all-atom steered molecular dynamics simulations. Uptake and internalization of rigid, few-layer graphene sheets disrupts the spatial organization of the filamentous actin (F-actin) cytoskeleton in macrophages in vitro (Figure 1).

Project 2, in collaboration with Project 4, will develop graphene-based environmental barriers in a responsible manner that considers both performance and potential adverse human health impacts throughout the design and evaluation phases. Project 2 will evaluate potential adverse human health impacts of novel graphene-based composite barriers developed in Project 4 for containment of vapor toxicants at Superfund and toxic waste sites.

Specific Aims

1. Determine the role of lateral dimension of GFNs on macrophage uptake, motility, and toxicity.
2. Systematically assess the effects of surface oxidation state and aging on ROS generation, toxicity, and biodurability of GFNs.
3. Evaluate the toxicity of complex graphene-copper hybrid materials.
4. Rank pristine, surface-modified, and complex metal-hybrid GFNs based on acellular and in vitro toxicity assays and validate this ranking by assessing toxicity and biopersistence of selected materials in 3-dimensional lung microtissues and in mice.

This integrated, interdisciplinary research approach will enable safe design and fabrication of GFNs for commercial applications and environmental remediation with minimal adverse human health impacts.

Project Leader

 Agnes Kane, M.D., Ph.D.
Agnes_Kane@brown.edu

 

Relevant Articles

Sanchez VC, Jachak A, Hurt RH, and Kane, AB. (2012). Biological Interactions of Graphene-Family Nanomaterials: An Interdisciplinary Review. Chemical Research in Toxicology, 25 (1), 15-34

Li Y, Yuan H., von dem Bussche A, Creighton M, Hurt RH, Kane AB, and Gao H. (2013). Graphene microsheets enter cells through spontaneous membrane penetration at edge asperities and corner sites. Proceedings of the National Academy of Sciences of the United States of America, 110(30), 12295–12300.