See the writing on the cells

U. MICHIGAN (US)—In the search for an efficient way to understand the roles of different genes, researchers have developed a technology that allows two water-based liquids to mingle without mixing, much like oil and water. The “micropatterning” method could prove useful in biological experiments.

“If you take a brush with watercolor paint and move it around in a dish of water, you usually just wash away the paint in the water and get no picture. That’s what happens with water-soluble biological reagents in typical cell culture experiments as well. The reagents just diffuse everywhere with no localization,” says Shuichi Takayama, associate professor of biomedical engineering and macromolecular science and engineering at the University of Michigan.

“But we have a system in which you can actually have aqueous solutions that don’t mix with each other. Rather than getting a murky dish of washed-away paint, we can create watercolor pictures at the bottom of a dish of water. And when the paint includes gene expression and silencing reagents, we can sketch biological experiments directly onto a canvas of living cells.”

Gene expression and silencing reagents are substances that tell cells in an experiment which genes to turn on or off.

Takayama and his colleagues were able to paint reagents on breast cancer cells to make them turn fluorescent proteins on and off in different patterns, and caused a group of cells in a layer of normally non-invasive cells to become invasive, like cancer cells, by turning on a particular gene.

“What would help is to be able to use smaller amounts of reagents and cells, to pack more experiments into the same area or plate of experiments, and to be able to study cells in complex microenvironments that mimic living organisms more than typical dishes do,” explains postdoctoral researcher Hossein Tavana. “Our technology, which provides the ability to localize nanoliter droplets of reagents over cells in high density arrays without the need to have segregating physical walls or the limits of having to print on a dry substrate, satisfies these needs.”

The new technology allows researchers to use hundreds of times less reagent than is used in comparable experiments under the current methods. Also, cells and reagents permanently remain in a wet environment, which is preferable.

“Life is about micropatterns,” Takayama says. “Tissues and organs and even living organisms are patterns of cells put together. All cells in our bodies have essentially the same DNA blueprint, but which genes are expressed or suppressed make a cell function as an eye or cheek or liver, or as a normal cell versus a cancer cell.

“Being able to pattern gene expression and silencing reagents on cells grown on native-like surfaces in a more efficient and versatile manner will help us better understand how living organisms function or how diseases like cancer progress.”

The National Institutes of Health supported the research, which was published online Aug. 16 in Nature Materials.

University of Michigan news: www.umich.edu/news

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