Origami Not Just for Paper Anymore: DNA, Folded Into Complex Shapes, Could Have a Big Impact on Nanotechnology

Trying to build DNA structures on a large scale was once considered unthinkable. But about five years ago, Caltech computational bioengineer Paul Rothemund laid out a new design strategy called DNA origami: the construction of two-dimensional shapes from a DNA strand folded over on itself and secured by short"staple" strands. Several years later, William Shih's lab at Harvard Medical School translated this concept to three dimensions, allowing design of complex curved and bent structures that opened new avenues for synthetic biological design at the nanoscale.

A major hurdle to these increasingly complex designs has been automation of the design process. Now a team at MIT, led by biological engineer Mark Bathe, has developed software that makes it easier to predict the three-dimensional shape that will result from a given DNA template. While the software doesn't fully automate the design process, it makes it considerably easier for designers to create complex 3-D structures, controlling their flexibility and potentially their folding stability.

"We ultimately seek a design tool where you can start with a picture of the complex three-dimensional shape of interest, and the algorithm searches for optimal sequence combinations," says Bathe, the Samuel A. Goldblith Assistant Professor of Applied Biology."In order to make this technology for nanoassembly available to the broader community -- including biologists, chemists, and materials scientists without expertise in the DNA origami technique -- the computational tool needs to be fully automated, with a minimum of human input or intervention."

Bathe and his colleagues described their new software in the Feb. 25 issue ofNature Methods. In that paper, they also provide a primer on creating DNA origami with collaborator Hendrik Dietz at the Technische Universitaet Muenchen."One bottleneck for making the technology more broadly useful is that only a small group of specialized researchers are trained in scaffolded DNA origami design," Bathe says.

Programming DNA

DNA consists of a string of four nucleotide bases known as A, T, G and C, which make the molecule easy to program. According to nature's rules, A binds only with T, and G only with C."With DNA, at the small scale, you can program these sequences to self-assemble and fold into a very specific final structure, with separate strands brought together to make larger-scale objects," Bathe says.

Rothemund's origami design strategy is based on the idea of getting a long strand of DNA to fold in two dimensions, as if laid on a flat surface. In his first paper outlining the method, he used a viral genome consisting of approximately 8,000 nucleotides to create 2-D stars, triangles and smiley faces.

That single strand of DNA serves as a"scaffold" for the rest of the structure. Hundreds of shorter strands, each about 20 to 40 bases in length, combine with the scaffold to hold it in its final, folded shape.

"DNA is in many ways better suited to self-assembly than proteins, whose physical properties are both difficult to control and sensitive to their environment," Bathe says.

Bathe's new software program interfaces with a software program from Shih's lab called caDNAno, which allows users to manually create scaffolded DNA origami from a two-dimensional layout. The new program, dubbed CanDo, takes caDNAno's 2-D blueprint and predicts the ultimate 3-D shape of the design. This resulting shape is often unintuitive, Bathe says, because DNA is a flexible object that twists, bends and stretches as it folds to form a complex 3-D shape.

According to Rothemund, the CanDo program should allow DNA origami designers to more thoroughly test their DNA structures and tweak them to fold correctly."While we have been able to design the shape of things, we have had no tools to easily design and analyze the stresses and strains in those shapes or to design them for specific purposes," he says.

At the molecular-level, stress in the double helix of DNA decreases the folding stability of the structure and introduces local defects, both of which have hampered progress in the scaffolded DNA origami field.

Postdoctoral researcher Do-Nyun Kim and graduate student Matthew Adendorff, both of the Bathe lab, are now furthering CanDo's capabilities and optimizing the scaffolded DNA origami design process.

Building nanoscale tools

Once scientists have a reliable way to assemble DNA structures, the next question is what to do with them. One application scientists are excited about is a"DNA carrier" that can transport drugs to specific destinations in the body such as tumors, where the carrier would release the cargo based on a specific chemical signal from the target cancer cell.

Another possible application of scaffolded DNA origami could help reproduce part of the light-harvesting apparatus of photosynthetic plant cells. Researchers hope to recreate that complex series of about 20 protein subunits, but to do that, components must be held together in specific positions and orientations. That's where DNA origami could come in.

"DNA origami enables the nanoscale construction of very precise architectural arrangements. Researchers are exploiting this unique property to pursue a number of applications at the nanoscale, including a synthetic photocell," Bathe says."While applications such as this are still quite far off on the horizon, we believe that predictive engineering software tools are essential for progress in this direction."

Novel applications may also grow out of a new competition being held at Harvard this summer, called BIOMOD. Undergraduate teams from about a dozen schools, including MIT, Harvard and Caltech, will try to design nanoscale biomolecules for robotics, computing and other applications.

In the meantime, Bathe is focusing on further developing CanDo to enable automated DNA origami design."Once you have an automated computational tool that allows you to design complex shapes in a precise way, I think we're in a much better position to exploit this technology for interesting applications," he says.

For DNA origami to have a broad impact, it needs to become routine to simply order up DNA parts to build any configuration you can dream up, Bathe says. He notes:"Once non-specialists can design arbitrary 3-D nanostructures using DNA origami, their imaginations can run free."

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Functioning Synapse Created Using Carbon Nanotubes: Devices Might Be Used in Brain Prostheses or Synthetic Brains

The team, which was led by Professor Alice Parker and Professor Chongwu Zhou in the USC Viterbi School of Engineering Ming Hsieh Department of Electrical Engineering, used an interdisciplinary approach combining circuit design with nanotechnology to address the complex problem of capturing brain function.

In a paper published in the proceedings of the IEEE/NIH 2011 Life Science Systems and Applications Workshop in April 2011, the Viterbi team detailed how they were able to use carbon nanotubes to create a synapse.

Carbon nanotubes are molecular carbon structures that are extremely small, with a diameter a million times smaller than a pencil point. These nanotubes can be used in electronic circuits, acting as metallic conductors or semiconductors.

"This is a necessary first step in the process," said Parker, who began the looking at the possibility of developing a synthetic brain in 2006."We wanted to answer the question: Can you build a circuit that would act like a neuron? The next step is even more complex. How can we build structures out of these circuits that mimic the function of the brain, which has 100 billion neurons and 10,000 synapses per neuron?"

Parker emphasized that the actual development of a synthetic brain, or even a functional brain area is decades away, and she said the next hurdle for the research centers on reproducing brain plasticity in the circuits.

The human brain continually produces new neurons, makes new connections and adapts throughout life, and creating this process through analog circuits will be a monumental task, according to Parker.

She believes the ongoing research of understanding the process of human intelligence could have long-term implications for everything from developing prosthetic nanotechnology that would heal traumatic brain injuries to developing intelligent, safe cars that would protect drivers in bold new ways.

For Jonathan Joshi, a USC Viterbi Ph.D. student who is a co-author of the paper, the interdisciplinary approach to the problem was key to the initial progress. Joshi said that working with Zhou and his group of nanotechnology researchers provided the ideal dynamic of circuit technology and nanotechnology.

"The interdisciplinary approach is the only approach that will lead to a solution. We need more than one type of engineer working on this solution," said Joshi."We should constantly be in search of new technologies to solve this problem."

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Fat Turns Into Soap in Sewers, Contributes to Overflows

"We found that FOG deposits in sewage collection systems are created by chemical reactions that turn the fatty acids from FOG into, basically, a huge lump of soap," says Dr. Joel Ducoste, a professor of civil, construction and environmental engineering at NC State and co-author of a paper describing the research. Collection systems are the pipes and pumping stations that carry wastewater from homes and businesses to sewage-treatment facilities.

These hardened FOG deposits reduce the flow of wastewater in the pipes, contributing to sewer overflows -- which can cause environmental and public-health problems and lead to costly fines and repairs.

The research team used a technique called Fourier Transform Infrared (FTIR) spectroscopy to determine what the FOG deposits were made of at the molecular level. FTIR spectroscopy shoots a sample material with infrared light at various wavelengths. Different molecular bonds vibrate in response to different wavelengths. By measuring which infrared wavelengths created vibrations in their FOG samples, researchers were able to determine each sample's molecular composition.

Using this technique, researchers confirmed that the hardened deposits were made of calcium-based fatty acid salts -- or soap.

"FOG itself cannot create these deposits," Ducoste says."The FOG must first be broken down into its constituent parts: glycerol and free fatty acids. These free fatty acids -- specifically, saturated fatty acids -- can react with calcium in the sewage collection system to form the hardened deposits.

"Until this point we did not know how these deposits were forming -- it was just a hypothesis," Ducoste says."Now we know what's going on with these really hard deposits."

The researchers are now focused on determining where the calcium in the collection system is coming from, and how quickly these deposits actually form. Once they've resolved those questions, Ducoste says, they will be able to create numerical models to predict where a sewage system may have"hot spots" that are particularly susceptible to these blockages.

Ultimately, Ducoste says,"if we know how -- and how quickly -- these deposits form, it may provide scientific data to support policy decisions related to preventing sewer overflows."

The research was funded by the Water Resources Research Institute and the U.S. Environmental Protection Agency.

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Pier Review: Comparing Ultra High-Resolution Photographs from the Past and the Present Could Hold the Key to Restoring Hastings' Fire-Damaged Pier

Prior to the fire, NPL, the UK's National Measurement Institute, had been surveying the pier to support redevelopment plans and to monitor long-term changes in the pier. The project was part of the development of a world leading low-cost technique to assess long-term degradation of structures.

The technique is called Digital Image Correlation. It has been used in the laboratory for some time but NPL have recently been pioneering its use for looking at civil engineering structures. It involves taking ultra high-resolution panoramic photos -- images up to 1.4 Giga Pixels in size -- at two different times to identify structural changes. Advanced mathematical programs then analyse the pair of images to identify changes in the structure pixel by pixel. Using this information, engineers can understand how large structures change over time.

Following the devastating fire, NPL scientists returned to Hastings to take their second set of photos. They were then required to develop more advanced analysis techniques, which could deal with the much larger than anticipated changes to the Pier, and produce meaningful information about the structure. This work is proving more valuable than expected as considerable change has now taken place. In addition, the large panoramic images provide a snapshot of the structure in time, which is useful for archival purposes.

Up to 45 images were stitched together to produce an ultra high-resolution final image 80,000 pixels wide -- 300-400 times more detailed than a typical camera-phone photograph. Processing a pair of these images, one before the fire and one after, can help highlight where the structure has apparently changed because of the fire.

Results have been very positive. Whilst the super-structure has been severely damaged and there are large visual changes, the cast iron framework -- or sub-structure -- seems much less affected. The sub-structure on the west side of the Pier appears to be remarkably similar pre and post fire. On the East side there are small areas where there are some changes, and one localised area of the sub-structure about half way along showing significant distortion. But the vast majority of the sub-structure seems largely unchanged. The area showing the most distortion -- presumably caused by the extreme heat -- was at a downwind point where anecdotally the fire was seen to be fiercest.

Digital Image Correlation allows the computer to effectively carry out the laborious checking of the whole structure. This means quicker and cheaper identification of areas which have been deformed or damaged, and hence may need closer inspection. This is important on large structures such as piers as it allows civil engineers to focus their efforts on the parts that most need attention, dramatically speeding the inspection process and reducing the cost of repair.

The project has also helped prove the concept of Digital Image Correlation for the measurement of changes in large structures, by providing NPL with a real-life case study enabling development of key analysis software.

Nick McCormick, Principle Research Scientist at NPL, said:"It was fortunate that we began the project before the fire, as the results will be invaluable in regenerating the pier when restoration funding is secured. From a scientific point of view, the scale of the changes actually proved very interesting, although challenging, and required us to develop far more advanced analysis techniques than originally intended. These will be hugely important in our work to develop low cost monitoring solutions for other structures. Obviously we hope the next one won't be so badly damaged part way through our study. For most applications we work on we would expect to monitor much less significant changes over time -- for example small cracks appearing in bridges or building subsidence -- so that problems can be remedied before they escalate to cause such serious damage."

Digital Image Correlation is one of a number of techniques that NPL is developing for low-cost examination of large civil engineering structures such as bridges, buildings, tunnels and piers.

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Carbon Fiber Used to Reinforce Buildings; Protect from Explosion

Sarah Orton, assistant professor of civil engineering in the MU College of Engineering, has focused on using carbon fiber reinforced polymer (CFRP), a fabric that can carry 143,000 pounds of force per square inch and has various applications to strengthen reinforced concrete buildings. CFRP has been used previously to strengthen buildings for earthquakes.

"CFRP has been used in places like California since the 1980s to protect buildings from earthquakes, but it has so many applications," Orton said."Now, we have to worry about damage caused by attacks. This fabric can be a great tool to protect people in threatened buildings."

To protect a building from an extreme event, CFRP can be used to increase the bending capacity of walls or columns. Previously, Orton invented an anchor that can be embedded in the column or joint to make CFRP more effective. In that work, Orton found that the anchors allow the CFRP to reach its full tension strength rather than separating from the concrete at only about half its strength.

CFRP can be used to protect an entire wall from an explosion. To study the effectiveness of different ways of applying CFRP, Orton worked with the U.S. Army Engineer Research and Development Center (ERDC) to detonate explosives near CFRP-reinforced concrete slabs. She found that CFRP, when layered and anchored, provided a significant amount of protection. However, she said that applying additional protection to the front of the concrete slab, such as a steel plate, would enhance the slab's performance.

Orton says the high costs of approximately$30 per square foot have kept CFRP from being widely implemented in non-earthquake prone areas.

"This is a really useful material," Orton said."I continue to be fascinated by the material's strength and applications. Retrofitting buildings with CFRP will help protect people from attacks and potentially collapse of the building."

The study,"Use of Carbon Fiber Anchors to Improve Performance of CFRP Strengthened Concrete Structures Subjected to Blast and Impact Loads," will be published in a special publication of the American Concrete Institute.

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Rainbow-Trapping Scientist Now Strives to Slow Light Waves Even Further

In a paper published March 29 in theProceedings of the National Academy of Sciences, Qiaoqiang Gan (pronounced"Chow-Chung" and"Gone"), PhD, an assistant professor of electrical engineering at the University at Buffalo's School of Engineering and Applied Sciences, and his colleagues at Lehigh University, where he was a graduate student, described how they slowed broadband light waves using a type of material called nanoplasmonic structures.

Gan explains that the ultimate goal is to achieve a breakthrough in optical communications called multiplexed, multiwavelength communications, where optical data can potentially be tamed at different wavelengths, thus greatly increasing processing and transmission capacity.

He notes that it is widely recognized that if light could ever be stopped entirely, new possibilities would open up for data storage.

"At the moment, processing data with optical signals is limited by how quickly the signal can be interpreted," he says."If the signal can be slowed, more information could be processed without overloading the system."

Gan and his colleagues created nanoplasmonic structures by making nanoscale grooves in metallic surfaces at different depths, which alters the materials' optical properties.

These plasmonic chips provide the critical connection between nanoelectronics and photonics, Gan explains, allowing these different types of devices to be integrated, a prerequisite for realizing the potential of optical computing,"lab-on-a-chip" biosensors and more efficient, thin-film photovoltaic materials.

According to Gan, the optical properties of the nanoplasmonic structures allow different wavelengths of light to be trapped at different positions in the structure, potentially allowing for optical data storage and enhanced nonlinear optics.

The structures Gan developed slow light down so much that they are able to trap multiple wavelengths of light on a single chip, whereas conventional methods can only trap a single wavelength in a narrow band.

"Light is usually very fast, but the structures I created can slow broadband light significantly," says Gan."It's as though I can hold the light in my hand."

That, Gan explains, is because of the structures' engineered surface"plasmon resonances," where light excites the waves of electrons that oscillate back and forth on metal surfaces.

In this case, he says, light can be slowed down and trapped in the vicinity of resonances in this novel, dispersive structural material.

Gan and his colleagues also found that because the nanoplasmonic structures they developed can trap very slow resonances of light, they can do so at room temperature, instead of at the ultracold temperatures that are required in conventional slow-light technologies.

"In the PNAS paper, we showed that we trapped red to green," explains Gan."Now we are working on trapping a broader wavelength, from red to blue. We want to trap the entire rainbow."

Gan, who was hired at UB under the UB 2020 strategic strength in Integrated Nanostructured Systems, will be working toward that goal, using the ultrafast light source in UB's Department of Electrical Engineering in the laboratory of UB professor and vice president for research Alexander N. Cartwright.

"This ultrafast light source will allow us to measure experimentally just how slow is the light that we have trapped in our nanoplasmonic structures," Gan explains."Once we know that, we will be able to demonstrate our capability to manipulate light through experiments and optimize the structure to slow the light further."

Co-authors with Gan on the study are Filbert Bertoli, Yongkang Gao, Yujie Ding, Kyle Wagner and Dmitri Vezenov, all of Lehigh University.

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New Research Advances Understanding of Lead Selenide Nanowires

Now, a research team at the University of Pennsylvania's schools of Engineering and Applied Science and Arts and Sciences has shown how to control the characteristics of semiconductor nanowires made of a promising material: lead selenide.

Led by Cherie Kagan, professor in the departments of Electrical and Systems Engineering, Materials Science and Engineering and Chemistry and co-director of Pennergy, Penn's center focused on developing alternative energy technologies, the team's research was primarily conducted by David Kim, a graduate student in the Materials Science and Engineering program.

The team's work was published online in the journalACS Nanoand will be featured in the Journal's April podcast.

The key contribution of the team's work has to do with controlling the conductive properties of lead selenide nanowires in circuitry. Semiconductors come in two types,nandp, referring to the negative or positive charge they can carry. The ones that move electrons, which have a negative charge, are called"n-type." Their"p-type" counterparts don't move protons but rather the absenceof an electron -- a"hole" -- which is the equivalent of moving a positive charge.

Before they are integrated into circuitry, the semiconductor nanowire must be"wired up" into a device. Metal electrodes must be placed on both ends to allow electricity to flow in and out; however, the"wiring" may influence the observed electrical characteristics of the nanowires, whether the device appears to ben-type orp-type. Contamination, even from air, can also influence the device type. Through rigorous air-free synthesis, purification and analysis, they kept the nanowires clean, allowing them to discover the unique properties of these lead selenide nanomaterials.

Researchers designed experiments allowing them to separate the influence of the metal"wiring" on the motion of electrons and holes from that of the behavior intrinsic to the lead selenide nanowires. By controlling the exposure of the semiconductor nanowire device to oxygen or the chemical hydrazine, they were able to change the conductive properties betweenp-type andn-type. Altering the duration and concentration of the exposure, the nanowire device type could be flipped back and forth.

"If you expose the surfaces of these structures, which are unique to nanoscale materials, you can make themp-type, you can make themn-type, and you can make them somewhere in between, where it can conduct both electrons and holes," Kagan said."This is what we call 'ambipolar.'"

Devices combining onen-type and onep-type semiconductor are used in many high-tech applications, ranging from the circuits of everyday electronics, to solar cells and thermoelectrics, which can convert heat into electricity.

"Thinking about how we can build these things and take advantage of the characteristics of nanoscale materials is really what this new understanding allows," Kagan said.

Figuring out the characteristics of nanoscale materials and their behavior in device structures are the first steps in looking forward to their applications.

These lead selenide nanowires are attractive because they may be synthesized by low-cost methods in large quantities.

"Compared to the big machinery you need to make other semiconductor devices, it's significantly cheaper," Kagan said."It doesn't look much more complicated than the hoods people would recognize from when they had to take chemistry lab."

In addition to the low cost, the manufacturing process for lead selenide nanowires is relatively easy and consistent.

"You don't have to go to high temperatures to get mass quantities of these high-quality lead selenide nanowires," Kim said."The techniques we use are high yield and high purity; we can use all of them."

And because the conductive qualities of the lead selenide nanowires can be changed while they are situated in a device, they have a wider range of functionality, unlike traditional silicon semiconductors, which must first be"doped" with other elements to make them"p" or"n."

The Penn team's work is a step toward integrating these nanomaterials in a range of electronic and optoelectronic devices, such as photo sensors.

The research was conducted by Kim and Kagan, along with Materials Science and Engineering undergraduate and graduate students Tarun R. Vemulkar and Soong Ju Oh; Weon-Kyu Koh, a graduate student in Chemistry; and Christopher B. Murray, a professor in Chemistry and in Materials Science and Engineering.

This work was supported with funding from the National Science Foundation Division of Materials Research, the National Science Foundation Solar Program and the National Science Foundation Nano-Bio Interface Center.

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Invisibility Cloaks and More: Force of Acoustical Waves Tapped for Metamaterials

Metamaterials are artificial materials that are engineered to have properties not found in nature. These materials usually gain their unusual properties -- such as negative refraction that enables subwavelength focusing, negative bulk modulus, and band gaps -- from structure rather than composition.

By creating an inexpensive bench-top technique, as described in the American Institute of Physics' journalReview of Scientific Instruments, Los Alamos National Lab (LANL) researchers are making these highly desirable metamaterials more accessible.

Their technique harnesses an acoustical wave force, which causes nano-sized particles to cluster in periodic patterns in a host fluid that is later solidified, explains Farid Mitri, a Director's Fellow, and member of the Sensors& Electrochemical Devices, Acoustics& Sensors Technology Team, at LANL.

"The periodicity of the pattern formed is tunable and almost any kind of particle material can be used, including: metal, insulator, semiconductor, piezoelectric, hollow or gas-filled sphere, nanotubes and nanowires," he elaborates.

The entire process of structure formation is very fast and takes anywhere from 10 seconds to 5 minutes. Mitri and colleagues believe this technique can be easily adapted for large-scale manufacturing and holds the potential to become a platform technology for the creation of a new class of materials with extensive flexibility in terms of periodicity (mm to nm) and the variety of materialsthat can be used.

"This new class of acoustically engineered materials can lead to the discovery of many emergent phenomena, understanding novel mechanisms for the control of material properties, and hybrid metamaterials," says Mitri.

Applications of the technology, to name only a few, include: invisibility cloaks to hide objects from radar and sonar detection, sub-wavelength focusing for production of high-resolution lenses for microscopes and medical ultrasound/optical imaging probes, miniature directional antennas, development of novel anisotropic semiconducting metamaterials for the construction of effective electromagnetic devices, biological scaffolding for tissue engineering, light guide, and a variety of sensors.

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