Built for speed: DNA nanomachines take a (rapid) step forward

May 8, 2018

When it comes to matching simplicity with staggering creative potential, DNA may hold the prize. Built from an alphabet of just four nucleic acids, DNA provides the floor plan from which all earthly life is constructed.

But DNA’s remarkable versatility doesn’t end there. Researchers have managed to coax segments of DNA into performing a host of useful tricks. Hao Yan, director of the Biodesign Center for Molecular Design and Biomimetics, and his colleagues have developed a walking robot constructed from sequences of DNA. The robot uses a cartwheeling motion to rapidly cover distance. The new innovation opens the door to other DNA nanotechnology innovations in electronics, materials science and medicine. Graphic by Zhuoru Li Download Full Image

DNA sequences can form logical circuits for nanoelectronic applications. They have been used to perform sophisticated mathematical computations, like finding the optimal path between multiple cities. And DNA is the basis for a new breed of tiny robots and nanomachines. Measuring thousands of times smaller than a bacterium, such devices can carry out a multitude of tasks.

In new research, Arizona State University Professor Hao Yan and his colleagues describe an innovative DNA walker, capable of rapidly traversing a prepared track. Rather than slow, tentative steps across a surface, the new DNA acrobat cartwheels head over heels, covering ground 10 to 100 times faster than previous devices.

“It is exciting to see that DNA walkers can increase their speed significantly by optimizing DNA strand length and sequences; the collaborative effort really made this happen,” Yan said.

The study was led by Nils G. Walter — the Francis S. Collins Collegiate Professor of Chemistry, Biophysics & Biological Chemistry, founding director of the Single Molecule Analysis in Real-Time (SMART) Center and founding co-director of the Center for RNA Biomedicine at the University of Michigan — and his team, along with collaborators from the Wyss Institute, the Dana Farber Cancer Institute and the Department of Biological Chemistry at Harvard (all in Boston).

“The trick was to make the walker go head over heels, which is so much faster than the hopping used before — just as you would see in a kung fu action movie where the hero speeds up by cartwheeling to catch the villain,” Walter said.

The improvements in speed and locomotion displayed by the new walker should encourage further innovations in the field of DNA nanotechnology.

The group’s findings appear in the advanced online issue of the journal Nature Nanotechnology.

Building with DNA

Nanoarchitects build their DNA structures, motors and circuits using the same basic principle as nature. The four nucleotides, labeled A, T, C and G, bind to each other according to a simple and predictable rule: Cs always pair with Gs, and As always pair with Ts. Thus, varying lengths of DNA may be programmed to self-assemble, snapping together to form an unlimited variety of two- and three-dimensional nanostructures. With clever refinement, researchers have been able to outfit their once-static nanocreations with dynamical properties.

One of the more innovative applications of DNA nanotechnology has been the design of robotic walking devices composed of DNA strands that successively move in a stepwise fashion across a path. The method enabling DNA segments to stroll across a defined area is known as strand displacement.

The process works like this: One leg of the robotic device is DNA strand 1, which is bound to complementary strand 2, through normal base pairing. Strand 1 contains an additional, unpaired sequence dangling from its end, which is known as the toehold.

Next, DNA strand 3 is encountered. This strand is complementary to DNA strand 1 and includes a toehold sequence complementary to DNA strand 1. Once the toehold of strand 3 binds with the toehold of strand 1, it begins sequentially displacing each strand 2 nucleotide, one by one, until strand 2 has been is completely replaced by strand 3. Strand 2 then dissociates from strand 1 and the process can begin again. (See graphic below).

Toehold-mediated strand displacement, which forms the basis of other DNA nanodevices, allows DNA structures to move from one complementary foothold on the walking surface to the next. As each DNA strand is displaced by a new strand, the nanocreature takes a step forward.

Hao Yan is the Milton D. Glick Distinguished Professor of Chemistry and Biochemistry at ASU and director of the Biodesign Center for Molecular Design and Biomimetics.

Race walking

Successful DNA walkers of various kinds have been designed and have demonstrated the ability to ferry nanosized cargo from place to place. Until now, however, the strand displacement reactions they rely on have been slow, generally requiring several minutes to move a short distance. This is much slower than naturally occurring processes in living systems like protein motors, which can perform feats of dissociation similar to strand displacement in much faster time frames.

While theoretical calculations suggest that individual operations by such nanodevices should occur in seconds or less, in practice, such operations typically require minutes or even hours. (A recently designed cargo-sorting walker, for example, required five minutes for each step, with foothold spacings just 6 nm apart. This speed was on a par with similar strand-displacement walkers.)

In the new study, researchers sought to optimize this process to see how quickly a walker designed with speed in mind could move. The limiting factor in terms of speed did not appear to be the strand displacement process itself, but rather the lack of fine-tuned optimization in the overall walker design.

The team redesigned their walker for maximum speed and used a fluorescent imaging technique known as smFRET (for single-molecule fluorescence resonance energy transfer) to chart the DNA walker’s progress and evaluate its subtle kinetic properties.

By altering the lengths of toehold sequences and branching migration points, the stepping rate could be keenly optimized, making for a briskly moving nanorobot that left competitors in the dust, boasting stepping rates a full order of magnitude faster than previous DNA walkers.

Dynamic DNA nanotechnology often makes use of toehold-mediated strand displacement reactions. In this example, the red strand binds to the single-stranded toehold region on the green strand (region 1), and then in a branch migration process across region 2, the blue strand is displaced and freed from the complex. Reactions like these are used to dynamically reconfigure or assemble nucleic acid nanostructures. In addition, the red and blue strands can be used as signals in a molecular logic gate. Credit: Antony-22 (Public domain)

Freewheeling nanorobot

Part of the robot’s advantage over its competitors is due to its unusual technique of locomotion. Rather than simply stepping from one surface foothold to the next, the acrobatic walker moves head over heels in a cartwheel fashion, while remaining securely bound to at least one foothold at all times.

The stability of the double-stranded sequences anchoring the base of the robot to the track surface, while the free toehold searches out the next complementary sequence, may be one factor improving the walker’s speed. The cartwheeling design also allows strand displacement to sequentially proceed in a direction away from the foothold surface, which improves efficiency.

Once the walker was optimized, super-resolved single particle tracking was used to observe the device’s movement over a 2D surface studded with footholds for the walker, covering a range of up to 2 microns. The best walker optimized in the study was able to search ~43 foothold sites per minute with a stepping distance of ~10 nm. Strand displacement occurred at rates of about a tenth of a second. Analysis suggests the device can take hundreds of steps without dissociating.

Future steps

While still lagging behind naturally occurring protein reactions, the optimized cartwheeling walker offers a marked advancement in performance, representing an order of magnitude improvement over earlier versions, while not consuming any fuel. Borrowing further insights from natural systems may allow dynamical DNA devices like the walker to accelerate even more in the future by converting chemical energy into directed speed.

The study underlines the opportunities for optimization of a range of DNA nanostructures, considerably enhancing their speed and versatility.

Richard Harth

Science writer, Biodesign Institute at ASU


ASU, EAC partnership sees largest graduating BSN cohort to date

May 8, 2018

This spring more than 400 College of Nursing and Health Innovation students are eligible to graduate, completing years’ worth of hard work and taking the next step in their lives and careers.

Among them is a cohort of 14 standout Bachelor of Science in nursing graduates who completed their degrees on a separate campus in a rural part of the state, thanks to a concurrent enrollment partnership with Eastern Arizona College. Graduates pose in their maroon caps and gowns on graduation day at the ASU Edson College of Nursing and Health Innovation building This partnership allows students who complete their associate degree at Eastern Arizona College to pursue a handful of Arizona State University bachelor’s degrees through classes offered in-person on EAC’s campus in the town of Thatcher, Arizona. Download Full Image

“It's a doable program that allows nursing students to pursue their bachelor’s degree at the same time as their associate degree from EAC,” Jesse Tapia said.

Tapia knows the program in and out; he’s one of the students graduating from it.

Each semester he took a couple of ASU courses on top of his EAC courses. It was not an easy path, especially because he was also balancing work and family.

In fact, Tapia said if it weren’t for the convenience and perhaps most importantly the reduced tuition, he may not have pursued the program at all.

“I’m able to graduate without needing student loans and I now have my bachelor’s degree in nursing which helps with job security and promotions!”

First announced in 2011, the partnership allows students who complete their associate degree at Eastern Arizona College to pursue a handful of Arizona State University bachelor’s degrees — like the BSN — through classes offered in-person on EAC’s campus in the town of Thatcher, Arizona.

“Many of them really would have a difficult time leaving this community to pursue a BSN because this is where their home is, it’s where their support system is and they want to stay here in this community,” said Carolyn Jo McCormies, nursing director and division chair at Eastern Arizona College.

Tapia said having ASU adjunct faculty on campus and being able to interact with them and his fellow classmates on a regular basis was key to his success.

“I like being able to meet my instructor and being able to ask questions in class. While a lot of the classwork was done online, we were able to meet in person, share ideas and experiences and help each other out,” he said.

Fellow BSN concurrent enrollment program graduate Samantha Jensen echoed that sentiment saying it was absolutely a perk to have that face-to-face opportunity with instructors.

She also really enjoyed the smaller class sizes.

“I believe I was able to get a more tailored education by staying in the town of Thatcher,” Jensen said.

Students are not the only ones reaping the rewards of this relationship. Patients in rural communities are benefitting too.

“By bringing the ASU education to students at EAC, we ensure they have the opportunity to reach a higher level of education that they can use to deliver excellent nursing care within their own communities,” said Heidi Sanborn, the interim director of the RN-BSN and Concurrent Enrollment Program and an assistant clinical professor for the College of Nursing and Health Innovation.

Sanborn works with McCormies and the College of Nursing and Health Innovaiton faculty on the Thatcher campus.

This partnership, Sanborn says is a solid example of the college's mission in action, which is to come up with innovative solutions to optimize the health and well-being of all our communities.

“This program ensures that ASU Bachelor of Science in nursing graduates stay right where they are needed, applying the knowledge gained in our program to communities far outside the reach of our downtown campus,” she said.

For the foreseeable future that’s the plan for several of these grads including Jensen, who will remain in the Eastern Arizona town.

While she did not grow up in Thatcher, she said she was raised in a community similar to it and because of that, her desire is to improve the health of those in rural communities.

Now that she’s getting her BSN Jensen said she definitely feels more prepared to enter the workforce.

“There were topics I learned throughout my bachelor courses that were not covered as deeply in my nursing program. I have a greater understanding of the health needs of my community and what my role is as a nurse in public health," she said.

As for Tapia, he says if you’re on the fence about the program like he was at first, do yourself a favor and really look into it.

“It’s an amazing program that gives a small-town college big opportunities to grow.”

Amanda Goodman

Senior communications specialist, Edson College of Nursing and Health Innovation