
If the results of the Brown toxicity study are confirmed by others, graphene could end up in the same hazardous-material category as its cylindrical relatives, carbon nanotubes.
"Graphene is easier to produce than carbon nanotubes and can replace them in many applications," Agnes Kane, a professor at Brown, told me:
- Graphene has many unique features, but most important is that it is often manufactured from graphite — a naturally occurring mineral — by chemical or mechanical exfoliation, which separates the carbon layers, resulting in dry powders with the potential for inhalation exposure. As a pathologist, we have studied nanotubes and other related carbon materials, but this is the first two-dimensional nanomaterial we’ve tested for toxicity.
The Brown research team led by Kane, chair of the school’s Department of Pathology and Laboratory Medicine, began with toxicity studies of graphene, which showed that indeed it did disrupt cell functions as nanotubes do. To discover why, Kane recruited a colleague in engineering for her team, professor Huajian Gao, who created atomically detailed computer simulations of the graphene material interacting with a living cell.
The mechanism discovered by the team was unexpected, since initial simulations of graphene interacting with living cells indicated it was benign. However, Kane’s biology group knew from toxicity experiments that graphene fragments did, in fact, interfere with normal functions in living cells. It turned out that first-generation simulations were too simple, modeling graphene fragments as squares, whereas real-world graphene fragments have sharp, pointy edges that can penetrate cell walls drawing the rest of the fragment inside after it. Gao’s revised simulations successfully modeled Kane’s toxicity experiments.

The sharp bottom corner of a piece of graphene (G) penetrating a cell membrane due to its nanoscale rough edges and sharp corners (scale bar is two microns).
(Source: Kane Lab / Brown University)
After the simulations revealed the mechanism by which graphene was interfering with normal cell function, Annette von dem Bussche, a professor of pathology and laboratory medicine, was able to repeat the toxicity experiments with detailed images that showed how the cells were being disrupted (see photo). The follow-up studies were performed on human lung, skin, and immune cells in Petri dishes, and confirmed that graphene sheets as large as 10 microns can pierce and be swallowed up by living cells.
All interesting nanomaterials have peculiar properties, and being declared hazardous does not doom a material, since many hazardous materials are already successfully used in semiconductor manufacturing, including lead, mercury, and cadmium. In fact, the Brown researchers are investigating a variety of nanomaterials for toxicity, as a prelude to developing safer methods of manufacturing, handling, and utilizing them throughout their lifecycles.
"The great thing about nanomaterials is that you can engineer them to have specific desirable properties," said Kane. "Using computational modeling, we hope to modify these materials to make them less toxic."
Graphene is considered a promising candidate to replace silicon in future semiconductors. Funding for the Brown research was provided by the National Science Foundation and the National Institute of Environmental Health Sciences. Robert Hurt, a professor of engineering, and doctoral candidates Yinfeng Li (now a professor at Shanghai Jiao Tong University), Hongyan Yuan, and Megan Creighton also contributed to the work.
