BROWN (US) — The jagged edges of tiny graphene sheets can spell trouble for human cells.
New research shows the sharp edges can puncture cell membranes. After the membrane is pierced, an entire graphene sheet can be pulled inside the cell where it may disrupt normal function.
The bottom corner of a piece of graphene penetrates a cell membrane. Mechanical properties—rough edges, sharp corners—can make graphene dangerous to human cells. Scale bar represents two microns. (Credit: Kane lab/Brown University)
The new insight may be helpful in finding ways to minimize the potential toxicity of graphene, says Agnes Kane, chair of the pathology and laboratory medicine department at Brown and one of the study’s authors.
“At a fundamental level, we want to understand the features of these materials that are responsible for how they interact with cells,” Kane adds. “If there’s some feature that is responsible for its toxicity, then maybe the engineers can engineer it out.”
The findings were published in the Proceedings of the National Academy of Sciences.
Is nanotech toxic?
Discovered about a decade ago, graphene is a sheet of carbon just one atom thick. It is incredibly strong despite being so thin and has remarkable electronic, mechanical, and photonic properties.
Commercial applications in small electronic devices, solar cells, batteries, and even medical devices are just around the corner. But not much is known about what effect these materials might have if they get inside 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,” says Robert Hurt, an engineering professor and one of the study’s authors. “So we want to understand how they interact with cells once inside the body.”
These latest findings come from an ongoing collaboration 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.
Oddly shaped flakes
Preliminary research by Kane’s biology group had shown that graphene sheets can indeed enter cells, but it wasn’t clear how they got there.
Huajian Gao, professor of engineering, tried to explain those results using powerful computer simulations, but he ran into a problem. His models, which simulate interactions between graphene and cell membranes at the molecular level, suggested 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 simply too high, even when the sheet hit edge first.
The problem turned out to be that those initial simulations assumed a perfectly square piece of graphene. In reality, graphene sheets are rarely so pristine.
When graphene is exfoliated, or peeled away from thicker chunks of graphite, the sheets come off in oddly shaped flakes with jagged protrusions called asperities. When Gao reran his simulations with asperities included, the sheets were able to pierce the membrane much more easily.
Under the microscope
Annette von dem Bussche, assistant professor of pathology and laboratory medicine, was able to verify the model experimentally. She placed human lung, skin, and immune cells in Petri dishes along with graphene microsheets.
Electron microscope images confirmed that graphene 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,” Kane says. “That allows us to better interpret the biological impacts of these materials. It’s really a wonderful collaboration.”
From here, the researchers will look in more detail into what happens once a graphene sheet gets inside the cell. But Kane says this initial study provides an important start in understanding the potential for graphene toxicity.
“This is about the safe design of nanomaterials,” she says. “They’re man-made materials, so we should be able to be clever and make them safer.”
Other contributors to the study were Brown graduate students Yinfeng Li (now a professor at Shanghai Jiao Tong University), Hongyan Yuan, and Megan Creighton. The National Science Foundation and the National Institute of Environmental Health Sciences funded the project.
Source: Brown University