"We cannot eat a lollipop longer than us," and our cells face similar limitations, according to an author of a recent paper that found that cells often try to engulf objects too large for them when they mistake them for more bite-sized nanomaterials.
The outsized nanomaterials — carbon nanotubes and asbestos fibers, which can sometimes be larger than the cells themselves — get stuck partway through the cell membrane, said the author, Huajian Gao, professor of engineering, who was a part of the team of Brown researchers behind the study, which was published Sunday in the journal Nature Nanotechnology.
Eating more than our fill is unhealthy, but people and cells still do it. The researchers set out to discover why cells bite off more than they can chew. Using scanning electron microscopy, they imaged mouse liver and human mesothelial cells exposed to one-dimensional nanomaterials, which entered the cells tip-first. Gao and his team hypothesized that the nanomaterials, by coming into contact with the cell membranes at wide angles, mimic small particles to initiate engulfment. Simulations confirmed that the nanomaterials were rotated to nearly a 90-degree angle before being ingested.
"This has to do with geometry … not chemistry," Gao said. No matter if asbestos fibers, gold nanowires or carbon nanotubes were used, "the cells mistake them for small spheres," he said. What these materials have in common, Gao explained, is a high aspect ratio, or outsize length relative to breadth.
The vertical alignment of the nanomaterials makes it impossible for the cell membrane to anticipate their length. So after initial wrapping of the material's tip by the cell membrane, engulfment discontinues — a process known as frustrated phagocytosis. The nanomaterial is left jutting out of the cell like a toothpick protruding from a morsel of cheese.
This incomplete job is toxic. Cells think that they are being attacked and call for help, causing inflammation. The rapid proliferation of cells increases the likelihood of mistakes being made in the copying of genetic material as cells divide. Such nanomaterials, which are often airborne, can escape out of laboratories or electronics and cause lung cancer in those exposed, Gao said.
The problem is, nanomaterials have many applications — in computer chips, as agents for drug delivery and in protecting space shuttles from the intense heat of the atmosphere. But as long as they're floating around in the air, they can cause our cells trouble. Gao said he and his team want to learn "to fully utilize their beneficial effects without causing harm to ourselves." The next stage of his research will be to study carbon graphene, a two-dimensional nanomaterial, to understand how it enters cells.
