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DNA twisted into pretzels

H. Dietz / TUM
This schematic shows some of the

nanoscale shapes made from DNA.

Click on the image for larger view.

Scientists are improving their technique for bending DNA into origami shapes. The latest twist uses custom-made chemicals to turn bunches of molecules into smoothly curving circlets and gears - a trick that eventually could set the stage for practical nanomachines.

DNA origami is a technique for folding the double helixes into programmed patterns. Some of the experiments have produced whimsical demonstrations such as a microscopic "happy face" or a map of the Americas. But the purpose behind all this is not mere child's play.

"Instead of just programming abstract software, we're programming matter," Harvard biochemist William Shih, one of the researchers behind the latest yoga tricks, told me today.

Shih and his colleagues - Harvard's Shawn Douglas and Hendrik Dietz of the Technische Universität München in Germany - report on their efforts in Friday's issue of the journal Science.

Previous tricks have taken advantage of angular bends in chemical bonds to create structures that "staple" themselves together with strands of DNA. In May, for example, Danish researchers unveiled nanoscale boxes made in this manner, complete with locks and keys.

This graphic shows how bundles of DNA molecules can be bent. Base pairs are removed from the orange strands of DNA, and added to the blue strands.

These new twists use the same type of readily available raw material: DNA from a virus that commonly infects bacteria, a critter known as M13.

The stapling technique, however, is different. Instead of twisting off at a sudden angle, the stapled-together bundles of DNA strands are chemically tweaked in such a way that base pairs are inserted in one strand, or removed in a different strand. In this way, the molecular bundles can be programmed to take on gradual curves or twists.

The biochemists behind the Science research did almost as good a job as Mother Nature: Inside the cell, DNA molecules can loop themselves into curls with a radius of about 4.5 nanometers. In comparison, the artificial structures had a minimum radius of 6 nanometers. Among the resulting shapes was a beachball-shaped latticework measuring just 50 nanometers wide.

The rounded curves and twists are the latest additions to a growing nanotech toolbox. "The DNA origami method is only three years old, so there hasn't been that much time for people to explore," Shih said. "We didn't realize how flexible, how malleable DNA is."

Now the big challenge is to reduce the defect rate for DNA self-assembly. Shih said his team's molecule-programming technique produces the desired shapes only 25 to 50 percent of the time. At the current scale, that's not such a problem, but if the technology is scaled up to create more complex structures, the defects would ruin any type of nanomachine you tried to make.

"We currently cannot build something intricate such as an ant's leg or, much smaller, a 10-nanometer-small chemical planet such as a protein enzyme," Dietz said in today's news release about the research. "We expect many benefits if only we could build super-miniaturized devices on the nanoscale using materials that work robustly in the cells of our bodies - biomolecules such as DNA."

One of the ways to reduce the defect rate might be to use biological processes rather than artificial chemistry to program the DNA molecules. "It's great chemistry, but you can't compete with enzymes," Shih explained.

"As engineers, we have to solve the same problems that nature has solved," he said. "We're optimistic that this will be possible."

Shih said he and his colleagues take their inspiration from the development of integrated-circuit technology, where small but steady advances have led to exponential increases in reliability and complexity.

He said the research has already yielded one piece of "low-lying fruit" - an artificially tweaked molecular structure that can shepherd protein molecules into a particular orientation for analysis. Once the protein molecules take on a non-random orientation, researchers can use nuclear magnetic resonance imaging to gain more information about how those molecules are folded. That could lead to better 3-D models for membrane protein structure, and better medications as well.

Looking farther down the road, Shih said nanomachines made from DNA could help build electronic (or plasmonic) circuitry, extending Moore's Law to molecular scales.

They could also deliver drugs or therapeutic genetic material directly into the cell. After all, the masters of molecular origami use DNA from a virus that does the same sort of thing for darker purposes.

"Things like viruses have evolved over millions of years to solve these problems," Shih said. "We'd like to be able to approach the efficiency with which viruses deliver their cargo to cells, but do it in a safer way."

More about nano-tricks:

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