Prions offer nanotech building tool

The same characteristics that make misfolded proteins known as prions such a pernicious medical threat in neurodegenerative diseases may offer a construction toolkit for manufacturing nanoscale electrical circuits, researchers report this week in the online edition of the Proceedings of the National Academy of Sciences.

Scientists working at Whitehead Institute for Biomedical Research and the University of Chicago write that they have used the durable, self-assembling fibers formed by prions as a template on which to deposit electricity-bearing gold and silver, creating electrical wire much thinner than it is possible to make by current mechanical processes.

“Most of the people working on nanocircuits are trying to build them using ’top-down’ fabrication techniques” used in conventional electrical engineering, explained Whitehead Institute Director Susan Lindquist, a co-author of the study. “We thought we’d try a ’bottom-up’ approach, and let molecular self-assembly do the hard work for us.”

Construction of nanoscale microcircuits and machines is one of the highly prized goals of nanotechnology. Manufacturing is very tricky at this scale – a nanometer is one-billionth of a meter; a nanometer is to a meter what a small grape would be to the entire Earth. Moreover, these devices depend on nanowires to conduct electricity. So far, the mass production of these tiny wires has stymied researchers. Making very small computers and optical switches, or even biomedical devices that could be inserted into the body, could open up whole new fields of computation and medicine.

Lindquist and her colleagues took a different approach. Rather than building the metal wire itself, they let prions build a very thin fibrous template and then coaxed gold and silver to bond to the protein fibers. By themselves, the fibers are insulators; they can’t conduct electricity. But when coated with gold and silver particles, they became remarkably effective electrical wires.

The choice of prions to build this template was a natural one for Lindquist and her colleagues at the University of Chicago, where she started work on this project before joining Whitehead Institute. Proteins are the cell’s workhorses, and they need to fold into complex and precise shapes to do their jobs. Prions are misfolded proteins – rather like an origami swan that comes out looking and acting instead like an ostrich.

Prions have another characteristic that makes them ideal for the mass-manufacturing jobs researchers have in mind: They recruit other, properly folded proteins into misforming along with them, a process Lindquist calls a “conformational cascade” that ends up producing more and more ostriches instead of swans.

In the test tube, conformational cascade generates strings and strings of tough, durable and heat-resistant protein fibers of a type known as “amyloid”. In humans, amyloids are best known as the plaque that gunks up neurons in people with Alzheimer’s, mad cow disease and other neurodegenerative illnesses. This may be one reason why these diseases are so resistant to treatment. However, yeast prions used as the source of protein in these experiments are completely harmless, making them safe to work with in manufacturing.

Lindquist and colleagues used a special genetic variant of yeast they modified to produce fibers capable of bonding with gold particles. They then coated these fiber strings with enough metal to make a working electrical wire.

In all important respects, these nanowires possess the characteristics of conventional solid metal wire, Lindquist explained, such as low resistance to electrical current.

“With materials like these,” she noted, “it should be possible to harness the extraordinary diversity and specificity of protein functions to nanoscale electrical circuitry.”

The research was supported by the National Institutes of Health, the W.M. Keck Foundation, the University of Chicago Materials Research Science and Engineering Center (MRSEC program of the NSF), the Howard Hughes Medical Institute and a postdoctoral fellowship of the Deutsche Forschungsgemeinschaft (T.S.).