Snappy DNA: Long strand folds into octahedron

DNA may embody the blueprint of life, but it could also be the stuff of future nanotechnologies. In a feat of molecular engineering, scientists recently designed a strand of DNA that can spontaneously fold into an octahedron.

DNA GEOMETRY. Visualization of a tiny octahedron made of DNA. M. Pique/Scripps Research Institute

Although scientists have made three-dimensional geometric shapes out of DNA before, those structures have readily deformed, says molecular biologist Gerald Joyce of the Scripps Research Institute in La Jolla, Calif. In contrast, his lab’s new octahedron is extremely rigid and could serve as a reliable nanoscale component. The structure has eight triangular faces and resembles two pyramids attached at their bases.

The rigidity of the octahedron comes not only from its overall geometry but also from the brawn of its 12 DNA struts. Each strut consists of two DNA stretches joined “like two ribbons wrapping around each other,” says Joyce.

To ensure that the DNA would spontaneously fold into the desired structure, Scripps team member William Shih first used computer software to come up with stretches of unique sequences of nucleotides, or DNA building blocks, that would bind together to form each strut. The final DNA strand contains close to 1,700 nucleotides.

When the researchers heated and cooled their DNA strands in a test tube, each one folded in on itself and snapped into a virus-size structure, 22 nanometers in diameter. Using a powerful electron microscope, the researchers confirmed that the structures were octahedral. “We zoomed in and saw them,” says Joyce. “That was a treat.”

The researchers describe their new structure in the Feb. 12 Nature.

“This is really beautiful work,” says Erik Winfree at the California Institute of Technology in Pasadena. Researchers have long wanted to assemble DNA structures using a single strand, he says, but “they just weren’t sure how.”

Nadrian Seeman at New York University built the first DNA nanostructure—a cube—more than a decade ago. Since then, researchers have used multiple DNA strands that require many-step assembly procedures to build various geometric shapes.

The advantage of creating a structure from a single piece of DNA is that it can be cloned, says Joyce. The Scripps team placed the DNA in bacteria, which replicated the fragment as the organisms multiplied. The researchers have also used an enzyme called polymerase to make exact copies of the DNA strands in a test tube.

In a laboratory version of evolution, the Scripps team plans to create variants of the octahedron’s DNA strand and place them in different environments to see which fare best. “You can start breeding for structure,” says Joyce. For example, if the researchers applied strand-breaking pressure to a collection of slightly different DNA octahedrons, only the strongest would remain intact.

The Scripps team is now designing octahedrons to serve as scaffolds for assembling materials or as hollow structures for carrying a cargo of proteins.

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