Small Wonder

This is a story about small things. But don’t be fooled into thinking that the measure of this work makes it inconsequential. Just like Mary Lou Retton, Mighty Mouse, and those tiny seeds that sit inside a jalapeño pepper, this work packs a punch.

In recent years, nanotechnology has been making headlines in both the scientific and popular press primarily because of its size. The fascination that many scientists find with nanoparticles—particles smaller than a quarter-millionth of an inch, or 1,000 times smaller than a human hair—may be attributed to the technology’s newness and unexplored power. The strength of the nanotech fervor has spread across research sectors ranging from pharmaceutical to fuel, and has resulted in the technology being identified as a mechanism for everything from faster prescription drug delivery in the human blood system to biofuel production. Yet, it is still new technology, and there are risks involved.

Yeast cultures, shown above in a petri dish, are used as a substitute for larger organisms in studies to track the impact of nanoparticles on living cells. Photo: Lynn Ketchum

In order to better understand and mitigate these risks, the U.S. Environmental Protection Agency granted almost $600,000 to two scientists in Oregon State University’s College of Agricultural Sciences for the study of nanotechnology and its impact on biology.

Manmade nanoparticles are specifically designed in laboratories to have commercially useful properties, but it is important to determine whether these useful properties produce adverse responses in animals or humans before they are commercialized, said Robert Tanguay, a researcher in OSU’s Department of Environmental and Molecular Toxicology and in the Oregon Nanoscience and Microtechnologies Institute.

“Because scientists have the ability to manipulate the properties of nanomaterials, it should be possible to engineer them to be useful components of consumer products with minimal harm to human health or the environment,” said Tanguay.

The work being done at OSU is helping to define how nanotechnology will be used to create new medicines, cosmetics, plastics, and even food. The research focuses on measuring the impact of manufactured nanomaterials on living systems like the human body.

A 15-hour-old zebrafish embryo (above) and adult zebrafish (below).The little, fast-growing fish are used to test the effects of nanoproducts on developing vertebrate embryos. Photos: Robert Tanguay

It is a lot like getting the mouse through the maze. Taking the first step in predicting nanomaterial–biological interactions, researchers in Tanguay’s laboratory are scanning a wide range of common nanomaterials to determine their potential interactions with biological systems. If they are found to produce adverse effects, the nanomaterial is identified along with its potential cellular or genetic target, and the particles are sorted by composition and effects. Connect the dots.

For more than a decade, Tanguay has used zebrafish—a small aquarium fish—to examine the effects of environmental contaminants and pharmaceuticals on early embryonic development. Zebrafish are vertebrates that are remarkably similar to humans at the molecular, genetic, and cellular levels, and many of the zebrafish findings are directly relevant to humans. Embryonic zebrafish are particularly useful for studying the effect of nanomaterial on living organisms because they develop quickly, are transparent, and can be easily maintained in small amounts of water.

“It is critical to couple the development of novel nanomaterials with the assessment of their effects on living organisms so society can move forward knowledgeably in the nanotechnology revolution,” said Tanguay.

To help engineer new and useful materials on the smallest scale, OSU researcher Robert Tanguay studies the effect of nanoproducts on developing zebrafish to determine adverse affects before the nanoproducts are developed for the market. Photo: Lynn Ketchum

Alan Bakalinsky is tackling an even smaller—or larger, depending on the point of view—issue concerning the role of manufactured nanomaterials and living systems. Bakalinsky, an OSU yeast biologist, and his colleagues in the Food Science and Technology Department are looking at the impact of these tiny materials on individual living cells.

Whether and how nanoparticles get into cells, and what happens to the cells as a result, are questions that Bakalinsky is hoping to answer. Cells are gigantic in comparison to nanomaterials, he said. Cells can be seen with a high-school microscope, but you need an electron microscope to see nanomaterials. The risk of interfering with cell function may be increased by this exaggerated size difference, as well as by the very small size and relatively large surface area of nanoparticles.

“Yeast shares a great number of functions with human and animal cells, and provides a very powerful model to look at cells,” - Alan Bakalinsky. Photo: Lynn Ketchum

“We’re trying to identify specific shapes and structures in manufactured nanoparticles that might cause damage to cells,” he said. “If we can determine which shapes and structures are most dangerous to cell function, it should be possible to design the materials to avoid those shapes and to minimize the risk of cell damage.”

Bakalinsky and Qilin Li, a collaborator on the project from Rice University, are using Saccharomyces cerevisiae—the common yeast used to make wine, beer, and bread—as the test subject in their research. They are focusing specifically on how the size and tendency of nanoparticles to clump together affects yeast survival.

“Yeast shares a great number of functions with human and animal cells and provides a very powerful model to look at cells,” said Bakalinsky. “It reproduces rapidly, is easily manipulated, and its entire genome was mapped years ago so we know exactly what we are looking at. We can pinpoint specific functions that affect how nanomaterials may or may not cause toxicity.”

This genomic approach will allow the researchers to pinpoint particular genes and proteins that may play key roles in protecting cells from damage caused by nanomaterials. Because many of these genes are also found in humans, much of what is learned about the yeast response to nanomaterials is expected to have direct relevance to how humans respond. The work is expected to lead to the development of safety guidelines for industrial and environmental exposure to nanomaterials.