Duke scientists ’program’ DNA molecules to self assemble into patterned nanostructures

Duke University researchers have used self-assembling DNA molecules as molecular building blocks called “tiles” to construct protein-bearing scaffolds and metal wires at the billionths of a meter, or “nanoscale.”

The achievements in nanoscale synthesis, which the five authors said could lead to programmable molecular scale sensors or electronic circuitry, were described in a paper in the Sept. 26, 2003, issue of the journal Science written by HaoYan, Thom LaBean, Gleb Finkelstein, Sung Ha Park and John Reif.

The Duke group’s research was funded by the National Science Foundation, the Defense Advanced Research Project Agency, and an industrial partners arrangement with Taiko Denki Co., Ltd. Fashioning protein nanoscaffolds and silver nanowires may be only the beginning, because tiles of this form “can be easily programmed by varying the sticky ends to form more sophisticated arrays,” the authors wrote.

“Our goal is to use DNA self-assembly to precisely control the location of other molecules,” said Yan, a molecular chemist working as an assistant research professor in Duke’s computer science department.

“The big promise is that if we can increase the size of our lattices we can template nanoelectronics onto them and make useful devices and circuits at a smaller scale than has ever been done before,” added LaBean, a molecular biologist who is also an assistant research professor of computer science.

Yan and LaBean are the tiles’ principal designers. Their work in DNA computation shows that the tiles’ self assembly into structures can be programmed, according to the researchers. “The tile itself is easy to modify by changing strands, so we can program the tile again and again for other purposes,” Yan said.

Because DNA strands naturally, but selectively, stick together, the Duke team reported in the Science paper that they could make the DNA strands arrange themselves into cross shaped “tiles” capable of forming molecular bonds on all four ends of the cross arms. As a result, large numbers of the crosses could naturally stick together to form semi-rigid waffle-patterned arrays that the authors called “stable and well behaved.”

Since two types of DNA component units called bases selectively pair up with the two others to form DNA strands — that is, adenine with thymine and guanine with cytosine — the scientists could exploit those biochemical properties to program different ways for their tiles to link together.

When the tiles were programmed to link with their faces all oriented in the same up or down direction, they self-assembled into narrow and long waffled “nanoribbons.” But when each tile’s face was programmed to point in the opposite direction from its neighbor, wider and broader waffled “nanogrids” were formed, the authors wrote.

In the case of the nanogrids, the authors found they could affix protein molecules to the cavities that the DNA tiles naturally formed at the center of each cross.

To affix the proteins, they first attached the chemical biotin to parts of the DNA strands they knew would self-assemble in the cavities. Then they added the protein streptavidin to the solution containing self assembled nanogrids. As a result, the biotin and streptavidin bound, in a reaction familiar to protein chemists. So complexes of protein molecules assembled atop those cavities.

“To use DNA self-assembly to template protein molecules or other molecules has been sought for years, and this is the first time it has been demonstrated so clearly,” said Yan. LaBean added that biomedical researchers could use such molecule-bearing nanogrids to detect other molecules. “Single molecule detection is one of the holy grails for sensors and diagnostics,” he said.

The researchers also used a two-step chemical procedure to coat silver onto the DNA nanoribbons to produce electrically-conducting nanowires. Assistant physics professor and nanoscientist Finkelstein, with graduate student Park, then deposited nanoscale metal connecting leads using a technique called electron beam lithography.

Building tiles of DNA arranged in angular shapes was pioneered in the laboratory of biochemist Nadrian “Ned” Seeman of New York University, where Yan earned his Ph.D. LaBean has collaborated for several years with Duke computer science professor Reif on designing DNA tiles for use as elements in biomolecular computation.

The idea of using the tiles as the equivalents of computing bits draws on the fact that DNA molecules stick together in predictable ways and can also, because of their nanoscale sizes, interact in extremely large numbers within small containers of solution.