Jagged edges of graphene can readily pierce cell membranes, letting graphene enter the cell and disrupt normal function, Brown University researchers have found. After the cell membrane is penetrated, an entire graphene sheet can be pulled inside the cell. This finding could help scientists find ways to minimize graphene’s potential toxicity.
“At a fundamental level, we want understand the features of these materials that are responsible for how they interact with cells. If there’s some feature that is responsible for its toxicity, then maybe the engineers can engineer it out,”
said Agnes Kane, one of the study’s authors.
One Atom Thick
Graphene, discovered around ten years ago, is a sheet of carbon just one atom thick. It is extremely strong even though it is so thin, and has astonishing electronic, mechanical, and photonic properties.
Commercial applications for graphene in small electronic devices, solar cells, batteries, and even medical devices are coming soon. However, little is known about what effect these materials might have if they enter the body either during the manufacturing process or during a product’s lifecycle.
“These materials can be inhaled unintentionally, or they may be intentionally injected or implanted as components of new biomedical technologies. So we want to understand how they interact with cells once inside the body,”
said engineering professor Robert Hurt.
Nanomaterials Toxic Potential
This latest insight comes from an ongoing partnership between biologists, engineers, and material scientists at Brown aimed at understanding the toxic potential of a wide variety of nanomaterials. Their work on graphene started with some seemingly contradictory findings.
Initial research by the biology group had shown that graphene sheets can enter cells, but it wasn’t known how they got there. Huajian Gao, a professor of engineering, tried to explain the results with computer simulations, but he had a problem.
His models, which simulate interactions between graphene and cell membranes at the molecular level, hinted that it would be quite rare for a microsheet to pierce a cell. The energy barrier required for a sheet to cut the membrane was too high, even when the sheet hit the edge first.
It turned out that his initial simulations were done assuming a perfectly square piece of graphene. But in practice, graphene sheets are rarely so perfect.
As graphene is peeled away from thicker chunks of graphite, the sheets come off in oddly shaped flakes with jagged protrusions known as asperities. When Gao reran his simulations including asperities, the sheets were able to pierce the membrane much more easily.
Experimental Verification
The model was then verified experimentally by assistant professor of pathology and laboratory medicine Annette von dem Bussche. She placed human skin, lung, and immune cells in Petri dishes along with graphene microsheets.
Electron microscope images confirmed that graphene indeed entered the cells starting at rough edges and corners. The experiments showed that even fairly large graphene sheets of up to 10 micrometers could be completely internalized by a cell.
“The engineers and the material scientists can analyze and describe these materials in great detail,” said Kane. “That allows us to better interpret the biological impacts of these materials. It’s really a wonderful collaboration.”
Going forward, the team will examine in detail what happens once a graphene sheet gets inside the cell. This initial study does, however, give them a good start in understanding the potential for graphene toxicity.
Reference: Yinfeng Li Hongyan Yuan, Annette von dem Bussche, Megan Creighton, Robert H. Hurt, Agnes B. Kane, and Huajian Gao Graphene microsheets enter cells through spontaneous membrane penetration at edge asperities and corner sites PNAS July 9, 2013 doi: 10.1073/pnas.1222276110
