Manipulated prions form basis for tiny electronic circuit- COUSIN TO DISEASE-CAUSING PROTEIN SUITED FOR WIRES

In a strange marriage of biology and electronics, researchers have turned prions — cousins of the infectious proteins that cause mad cow disease and other ailments — into tiny wires coated with silver and gold.

By Glennda Chui
Mercury News

No, the wires will not make you sick. This particular prion is a good guy, taken from the same common yeast that makes bread rise and beer ferment. It helps the yeast adapt to the outside world in ways that scientists are just starting to understand — an intriguing story in its own right.

But the prion does have one trait in common with its disease-causing relatives: It’s very hardy. It can withstand extreme heat and cold, as well as exposure to salt, acid and solvents.

That could make it an excellent building block for the teensy wires and electronic circuits that are a prime goal of nanotechnology.

“It’s really exciting stuff,” said Joel M. Schnur, director of the Center for Bio/Molecular Science and Engineering at the Naval Research Laboratory in Washington, D.C. He was not involved in the study.

The finding was reported Monday by Susan L. Lindquist, director of the Whitehead Institute for Biomedical Research in Cambridge, Mass., and colleagues at the University of Chicago.

Writing in the Proceedings of the National Academy of Sciences, they said the wires they made were 80 to 200 nanometers wide and good conductors of electricity.

Because the wires are formed around cores of protein fiber, they added, it should be possible to modify them in interesting ways, creating electronic circuits that assemble themselves, the way living things do.

Nanotechnology refers to the manufacture of computer chips and other devices on the scale of molecules, measured in billionths of a meter. One nanometer is as long as 10 hydrogen atoms strung together.

Working backward

“Most of the people working on nanocircuits are trying to build them using top-down fabrication techniques,” like those now used in manufacturing electronics, Lindquist said. “We thought we’d try a bottom-up approach, and let molecular self-assembly do the hard work for us.”

Hers is not the only team taking this tack. Scientists are looking at a number of biological molecules as templates for building small things — from the genetic material DNA to fats, viruses and the small, glassy shards of silica that stiffen the inside of a sponge.

The human body — or any organism, for that matter — is full of examples of self-assembly: Molecules organize themselves into cells, cells into tissues, tissues into organs and so on, Schnur said. “You can learn a lot from how evolution has solved these problems and try to tinker with that for your own purposes.”

In the case of the yeast prion, evolution has honed its capabilities for hundreds of millions of years, with surprising results.

Prions are notorious for causing rare disorders that turn the brain to sponge. The best-known are kuru, contracted by Papua New Guinea natives during ritual cannibalism; bovine spongiform encephalopathy, or mad cow disease, in cattle; and Creutzfeldt-Jakob disease in humans. A new variant of Creutzfeldt-Jakob cropped up in Europe in 1996 among people who ate meat from mad cows. There is no treatment for these conditions.

Unlike other things that we consider germs, prions are not viruses or bacteria. They are proteins, the ubiquitous building blocks of life.

Proteins can’t do their work unless they are folded into exactly the right shape. These shapes can be quite complex, in some cases resembling tumbleweeds.

The trouble with prion proteins is that they can suddenly change shape — and the new shape often changes the proteins’ effects. Once the proteins flip into this new configuration, they induce other proteins to flip, too.

In the case of prions that cause brain ailments such as mad cow disease, this chain reaction results in a buildup of abnormal proteins in the brain, causing neurological havoc. The infection can also spread to new hosts.

For a long time, researchers thought all prions were bad news. However in 1994, Dr. Reed Wickner of the National Institute of Diabetes and Digestive and Kidney Diseases discovered that the common beer-and-bread yeast, Saccharomyces cerevisiae, contains prions that appear to be harmless. These prions are passed on to future generations, creating a way of passing on traits that is not directly based on the genetic material DNA.

Ten of these prions have now been identified in yeast, Lindquist said. They may help the yeast survive by offering it a way to respond to changes in the environment. Although yeast prions don’t flip into their alternative form very often — it happens in only one in a million cells — there is a slight chance that the new form will give a cell a small advantage, such as an enhanced ability to survive infection by an invading fungus.

The 10 known yeast prions may act in combination, each affecting a particular function of the cell. Together, they may give yeast a lot more flexibility than its genetics alone could provide, Lindquist said.

Lindquist said harmless prions have been found in some fungi, but not in other organisms. However, she said she thinks it’s likely they will also be found in mammal cells. If so, they could influence all sorts of biological processes.

“I would place a very large bet on it,” she said. “I wouldn’t bet one of my children, but I would bet my car and my house. We think the same process may actually underlie a lot of normal biology.”

Long, skinny fibers

About three years ago, Linquist and her team, including physicists Heinrich Jaeger, Raghuveer Parthasarathy and Xiao-Min Lin and biologist Thomas Scheibel of the University of Chicago, began to explore the idea of turning one of the yeast prions into wires.

This particular prion spontaneously joins with others to form long, skinny fibers, nine to 11 nanometers wide, that are exceptionally tough and strong, the researchers said.

The team genetically modified the fibers in a way that made them attractive to gold particles. Then they coated the fibers with alternating layers of gold and silver until they had wires that were 80 to 100 nanometers wide.

The final diameter could be easily controlled, the scientists reported, and the resulting wires were very stable, making them good candidates to survive the kinds of manufacturing processes that are needed to produce electronic devices.

Contact Glennda Chui at [email protected] or (408) 920-5453.

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