ASU scientists develop innovative twists to DNA nanotechnology


March 21, 2013

In a new discovery that represents a major step in solving a critical design challenge, Arizona State University Professor Hao Yan has led a research team to produce a wide variety of 2-D and 3-D structures that push the boundaries of the burgeoning field of DNA nanotechnology.

The field of DNA nanotechnology utilizes nature's design rules and the chemical properties of DNA to self-assemble into an increasingly complex menagerie of molecules for biomedical and electronic applications. Some of the Yan lab's accomplishments include building Trojan horse-like structures to improve drug delivery to cancerous cells, electrically conductive gold nanowires, single molecule sensors and programmable molecular robots. Scientist twist DNA to make new nano structures Download Full Image

With their bio-inspired architectural works, the group continues to explore the geometrical and physical limits of building at the molecular level.

"People in this field are very interested in making wire frame or mesh structures," said Yan. "We needed to come up with new design principles that allow us to build with more complexity in three dimensions."

In their latest twist to the technology, Yan's team made new 2-D and 3-D objects that look like wire-frame art of spheres as well as molecular tweezers, scissors, a screw, hand fan, and even a spider web.

The Yan lab, which includes ASU Biodesign Institute colleagues Dongran Han, Suchetan Pal, Shuoxing Jiang, Jeanette Nangreave and assistant professor Yan Liu, published their results in the March 22 issue of Science.

The twist in their 'bottom up,' molecular Lego design strategy focuses on a DNA structure called a Holliday junction.

In nature, this cross-shaped, double-stacked DNA structure is like the 4-way traffic stop of genetics – where 2 separate DNA helices temporality meet to exchange genetic information. The Holliday junction is the crossroads responsible for the diversity of life on Earth, and ensures that children are given a unique shuffling of traits from a mother and father's DNA.

In nature, the Holliday junction twists the double-stacked strands of DNA at an angle of about 60-degrees, which is perfect for swapping genes but sometimes frustrating for DNA nanotechnology scientists, because it limits the design rules of their structures.

"In principal, you can use the scaffold to connect multiple layers horizontally," [which many research teams have utilized since the development of DNA origami by Cal Tech's Paul Rothemund in 2006]. However, when you go in the vertical direction, the polarity of DNA prevents you from making multiple layers," said Yan. "What we needed to do is rotate the angle and force it to connect."

Making the new structures that Yan envisioned required re-engineering the Holliday junction by flipping and rotating around the junction point about half a clock face, or 150 degrees. Such a feat has not been considered in existing designs.

"The initial idea was the hardest part," said Yan. "Your mind doesn't always see the possibilities so you forget about it. We had to break the conceptual barrier that this could happen."

In the new study, by varying the length of the DNA between each Holliday junction, they could force the geometry at the Holliday junctions into an unconventional rearrangement, making the junctions more flexible to build for the first time in the vertical dimension. Yan calls the backyard barbeque grill-shaped structure a DNA Gridiron.

"We were amazed that it worked!" said Yan. "Once we saw that it actually worked, it was relatively easy to implement new designs. Now it seems easy in hindsight. If your mindset is limited by the conventional rules, it's really hard to take the next step. Once you take that step, it becomes so obvious."

The DNA Gridiron designs are programmed into a viral DNA, where a spaghetti-shaped single strand of DNA is spit out and folded together with the help of small 'staple' strands of DNA that help mold the final DNA structure. In a test tube, the mixture is heated, then rapidly cooled, and everything self-assembles and molds into the final shape once cooled. Next, using sophisticated AFM and TEM imaging technology, they are able to examine the shapes and sizes of the final products and determine that they had formed correctly.

This approach has allowed them to build multilayered, 3-D structures and curved objects for new applications.

"Most of our research team is now devoted toward finding new applications for this basic toolkit we are making," said Yan. "There is still a long way to go and a lot of new ideas to explore. We just need to keep talking to biologists, physicists and engineers to understand and meet their needs."

Yan's research is funded by several grants from the National Science Foundation, Office of Naval Research, Army Research Office grant and an Army Research Office MURI award, and an ASU Presidential Strategic Initiative Fund. Hao Yan and Yan Liu are part of the Center for Bio-Inspired Solar Fuel Production, an Energy Frontier Research Center funded by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences.

Hao Yan is the Milton Glick Chair in the Department of Chemistry and Biochemistry and researcher at ASU's Biodesign Institute.

Joe Caspermeyer

Managing editor, Biodesign Institute

480-258-8972

Sun Devils move on to 2nd round of NIT


March 21, 2013

It might be the NIT, but the Sun Devils came to play as if they were a part of the NCAA Tournament.

Piggybacking off one of its best first half performances of the season, taking a 46-27 lead into the locker room, ASU never showed sign of weakness as it handled Detroit from start to finish, going on to bounce the Titans, 83-68. Download Full Image

The Sun Devils move on to the second round, where they will travel to Waco, Texas to face the Baylor Bears for a 5 p.m. (PT) tipoff, March 22.

Jahii Carson and Carrick Felix took over the heavy lifting for ASU, as Carson finished with 22 points to Felix's 21, despite getting in foul trouble midway through the second half. Carson, who shot 7-10 and 8-10 from the free throw line, also added 10 rebounds to notch a double-double. He missed a triple-double by three assists, as he had seven dimes on the night.

Felix also shot the ball well, finishing 8-13 from the field and 5-6 from the free throw line. He also had seven rebounds.

As a team, Arizona State shot 55 percent on 27-49 shooting, compared to Detroit, who shot 34 percent on 20-58 shooting from the field. A big factor in the contest came on the boards, as ASU out-rebounded the Titans by 20, 41-21. 

The Sun Devils got off to a monstrous start to begin the game, jumping out to an early 18-4 run thanks to early 7-10 shooting, while Detroit could not find a basket deep into the contest. They began the game shooting 0-6, and were forced to call a timeout with 13:17 to play, still searching for a basket.

Detroit's first six points came from the free throw line, two of which ended a Sun Devils' 14-0 scoring run.

By the time the Titans hit their first shot, with 10:14 to play in the half, ASU held a commanding 24-8 lead. Detroit officially began the game shooting 0-10 before getting its first basket to fall through. During that span, the Devils out-rebounded the Titans 17-2, including seven offensive rebounds to their one, to go along with an 11-0 second-chance points advantage.

At the official timeout with 7:52 to play, Arizona State still assumed a large 20-point lead, 30-10, showing no signs of slowing down its up-tempo pace.

Detroit welcomed the halftime buzzer, down 46-27, feeling fortunate the deficit was not any greater. Felix and Carson tormented the Titans throughout the half, finishing a combined 9-12 from the field. Felix completed the first 20 minutes of play with 15 points on 5-7 shooting to go along with five rebounds, while also connecting on 5-6 of his free throws. Carson also finished the half in double figures, scoring 12 points on 4-5 shooting. The point guard also led the team in rebounding at the break, notching seven.

While ASU shot a quality 58.3 percent on 14-24 shooting over the first half of play, Detroit's shooting percentage proved to be anything but. They finished at a dismal 22.2 percent on 6-27 shooting. The Titans survived by going 15-15 from the charity stripe, but the Sun Devils equalized by going 16-20 themselves.

Arizona State out-rebounded Detroit 27-6 in the first half.

Coming out of the locker room, however, the Sun Devils struggled to find the same hop to their step they had throughout the first half, allowing Detroit to move to within ten points with 16:59 to play thanks to a Nick Minnerath three-pointer.

With 14:11 to play, the Titans cut the lead to single digits for the first time since early in the first half, with the score 51-42. However, back-to-back buckets by Carson re-extended the lead to 13, as the two squads began trading baskets.

Finally able to put a string of points together, the Sun Devils put up six-straight of their own, regaining a 17-point advantage, 65-48, with 8:02 to play.

After a beautiful bounce pass from Carson through multiple defenders to Felix, who laid it up and under for two, ASU led by 17 with 3:46 to play, signaling to the crowd it would be all right for them to head to their vehicles.

With another victory, Arizona State tacked up its 22nd victory on the season, improving to 22-12.

Juno Schaser

Event coordinator, Biodesign Institute

480-965-0014