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DNA folded into a world of patterns

A computer scientist has developed a method to weave stringy DNA molecules into tiny two-dimensional patterns ranging from smiley faces to a map of the Americas.

A computer scientist has developed a method to weave stringy DNA molecules into nanometer-scale, two-dimensional patterns ranging from smiley faces to a map of the Americas.

Experts say the "DNA origami" procedure laid out by Paul Rothemund of the California Institute of Technology could be adapted to create nano-computers, new drug delivery systems or even molecular-scale chemical factories.

"We are arriving at a new frontier in our pursuit of ever-smaller structures," Lloyd Smith, a chemist at the University of Wisconsin at Madison, said in Thursday's issue of the journal Nature, where Rothemund's research was published.

In a news release, Rothemund said the process is so simple that high-school students should be able to design woven DNA patterns, but so versatile that scientists could build complex structures for a wide variety of nanotechnology applications.

"A physicist, for example, might attach nano-sized semiconductor 'quantum dots' in a pattern that creates a quantum computer," he said. "A biologist might use DNA origami to take proteins which normally occur separately in nature, and organize them into a multi-enzyme factory that hands a chemical product from one enzyme machine to the next in the manner of an assembly line."

Rothemund's technique uses chemicals to twist a long, single-stranded DNA molecule into a predetermined shape, then "staples" the scaffolding together with crossover strands. For the experiments reported in Nature, Rothemund used the genome from a bacteria-destroying virus called M13 — well-suited as weaving material because its 7,000-nucleotide sequence has been fully decoded.

An army of smileys
To demonstrate the technique's versatility, Rothemund created a variety of fanciful shapes, including stars, tilelike octagons that look like lace doilies, and squares of carpet with the letters "DNA," a double helix or the rough shapes of North and South America woven into it. The shapes range around 100 nanometers wide, about 1,000 times smaller than the diameter of a human hair.

One atomic-force microscopy image shows myriads of smiley faces bunching up under the microscope — which Smith called "a disconcerting sight."

Smith noted that the technique could allow for dyes or attachment points to be woven into the patterns. That could turn the origami patterns into "nano-breadboards" that would serve as the basis for molecular-scale circuitry.

Rothemund and other researchers are working to extend the 2-D origami technique to 3-D structures as well. If they're successful, that could lead to the development of 3-D molecular "cages" to hold enzymes or drug molecules. The tiny cages could be flipped open chemically when the material is needed.

Decades of research
Rothemund's work builds on decades of research into using DNA as a molecular-scale construction kit — a pursuit pioneered by New York University's Nadrian Seeman.

Seeman and his colleagues have been working with even smaller DNA structures in three dimensions, measuring mere nanometers in width rather than the tens of nanometers spanned by Rothemund's structures.

Seeman told that he was enthusiastic about Rothemund's work because it adds another level of scale to nano-construction processes.

"On a slightly larger scale, he's added a huge amount of convenience, and there's something to be said for that," Seeman said. The two techniques both take a "bottom-up" approach to creating small-scale structures, but Rothemund's origami method "might ultimately be easier to interface with the top-down world than ours."

Seeman emphasized that a variety of methods on a variety of scales will come into play as researchers develop nanostructures — just as tweezers, pliers and pipe wrenches are all useful at larger scales.