Design Rules Will Enable Scientists to Use DNA to Build Nanomaterials With Desired Properties

Design Rules Will Enable Scientists to Use DNA to Build Nanomaterials With Desired Properties

  12:35:00 AM    Science Lover

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Nature is a master builder. Using a bottom-up approach, nature takes tiny atoms and, through chemical bonding, makes crystalline materials, like diamonds, silicon and even table salt. In all of them, the properties of the crystals depend upon the type and arrangement of atoms within the crystalline lattice.

Abstract rendering of a DNA strand.
(Credit: iStockphoto/Johan Swanepoel)

Now, a team of Northwestern University scientists has learned how to top nature by building crystalline materials from nanoparticles and DNA, the same material that defines the genetic code for all living organisms.

Using nanoparticles as "atoms" and DNA as "bonds," the scientists have learned how to create crystals with the particles arranged in the same types of atomic lattice configurations as some found in nature, but they also have built completely new structures that have no naturally occurring mineral counterpart.

The basic design rules the Northwestern scientists have established for this approach to nanoparticle assembly promise the possibility of creating a variety of new materials that could be useful in catalysis, electronics, optics, biomedicine and energy generation, storage and conversion technologies.

The new method and design rules for making crystalline materials from nanostructures and DNA will be published Oct. 14 by the journal Science.

"We are building a new periodic table of sorts," said Professor Chad A. Mirkin, who led the research. "Using these new design rules and nanoparticles as 'artificial atoms,' we have developed modes of controlled crystallization that are, in many respects, more powerful than the way nature and chemists make crystalline materials from atoms. By controlling the size, shape, type and location of nanoparticles within a given lattice, we can make completely new materials and arrangements of particles, not just what nature dictates."

Mirkin is the George B. Rathmann Professor of Chemistry in the Weinberg College of Arts and Sciences and professor of medicine, chemical and biological engineering, biomedical engineering and materials science and engineering and director of Northwestern's International Institute for Nanotechnology (IIN).

"Once we have a certain type of lattice," Mirkin said, "the particles can be moved closer together or farther apart by changing the length of the interconnecting DNA, thereby providing near-infinite tunability."

"This work resulted from an interdisciplinary collaboration that coupled synthetic chemistry with theoretical model building," said coauthor George C. Schatz, a theoretician and the Charles E. and Emma H. Morrison Professor of Chemistry at Northwestern. "It was the back and forth between synthesis and theory that was crucial to the development of the design rules. Collaboration is a special aspect of research at Northwestern, and it worked very effectively for this project."



In the study, the researchers start with two solutions of nanoparticles coated with single-stranded DNA. They then add DNA strands that bind to these DNA-functionalized particles, which then present a large number of DNA "sticky ends" at a controlled distance from the particle surface; these sticky ends then bind to the sticky ends of adjacent particles, forming a macroscopic arrangement of nanoparticles.

Different crystal structures are achieved by using different combinations of nanoparticles (with varying sizes) and DNA linker strands (with controllable lengths). After a process of mixing and heating, the assembled particles transition from an initially disordered state to one where every particle is precisely located according to a crystal lattice structure. The process is analogous to how ordered atomic crystals are formed.

The researchers report six design rules that can be used to predict the relative stability of different structures for a given set of nanoparticle sizes and DNA lengths. In the paper, they use these rules to prepare 41 different crystal structures with nine distinct crystal symmetries. However, the design rules outline a strategy to independently adjust each of the relevant crystallographic parameters, including particle size (varied from 5 to 60 nanometers), crystal symmetry and lattice parameters (which can range from 20 to 150 nanometers). This means that these 41 crystals are just a small example of the near infinite number of lattices that could be created using different nanoparticles and DNA strands.

Mirkin and his team used gold nanoparticles in their work but note that their method also can be applied to nanoparticles of other chemical compositions. Both the type of nanoparticle assembled and the symmetry of the assembled structure contribute to the properties of a lattice, making this method an ideal means to create materials with predictable and controllable physical properties.

Mirkin believes that, one day soon, software will be created that allows scientists to pick the particle and DNA pairs required to make almost any structure on demand.

The Air Force Office of Scientific Research, the U.S. Department of Energy Office of Basic Energy Sciences and the National Science Foundation supported the research.

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Pi enthusiast calculates it to ten trillion digits

Pi enthusiast calculates it to ten trillion digits

  10:01:00 AM    Science Lover

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Shigeru Kondo is a seriously committed guy. Ever since discovering he had an interest in calculating pi (aka π) back in his college days, he’s been following the results achieved by others using massive supercomputers. Now, in his late 50's, with some help from Northwestern University grad school student Alexander Yee, he’s succeeded in calculating pi to ten trillion digits; on a home built PC yet.

Pi, the mathematical constant that describes the ratio of a circle’s circumference to its diameter, is generally rounded off to just two places, bringing it to 3.14. Believed to have been first described by Archimedes way back in the 3rd century BC, the ratio is used in all sorts of mathematical computations, not the least of which is in figuring out the area of a circle. But because pi is an irrational number, it’s value cannot be written as an fraction which means when written as a decimal approximation, it’s numbers go on infinitely, and perhaps more importantly, never repeat.

For hundreds of years, pi has held fascination for mathematicians, scientists, philosophers and even regular run of the mill people. Why this is so is hard to say, and so too is the seemingly endless progression of people that have set before themselves the task of calculating its digits. In spite of that, it’s possible that none has ever been so obsessed as Kondo. He’s spent the better part of a year with the singular task of finding the ten trillionth digit, and of course all those past the five trillionth and one digit leading up to the ten trillionth, since he found the five trillionth digit just last year.

Finding the value of pi to 10 trillion digits requires performing a lot of calculations (using software written by Yee), so many in fact, that Kondo had to add a lot more hard drive space than you’d find on your average PC. Forty eight terabytes to be exact. So intense was the computation that the computer alone caused the temperature in the room to hold steady at 104° F.

Also, it’s not as easy to keep a custom built super-sized PC going full steam ahead twenty four hours day for months on end, as it might seem. Hard drive failures and the threat of power disruption from the earthquake in Japan back in March threatened the project many times. And of course there was that power bill itself which ran to something close to $400 a month as the computer ground away.

But in the end, it was Kondo’s persistence that paid off. For his efforts he will be forever known (in the annals of science, and probably the Guinness Book of World Records) as the man who calculated the ten trillionth digit of pi. It’s 5.

More information: http://www.numberworld.org/misc_runs/pi-10t/details.html
http://ja0hxv.calico.jp/pai/estart.html

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That Late-night Snack: Worse Than You Think

That Late-night Snack: Worse Than You Think

  9:12:00 PM    Science Lover

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Eat less, exercise more. Now there is new evidence to support adding another "must" to the weight-loss mantra: eat at the right time of day.

Eating at irregular times -- the equivalent of the middle of the night for humans,
when the body wants to sleep -- influences weight gain, a new study has found.
(Credit: iStockphoto/Curt Pickens)

A Northwestern University study has found that eating at irregular times -- the equivalent of the middle of the night for humans, when the body wants to sleep -- influences weight gain. The regulation of energy by the body's circadian rhythms may play a significant role. The study is the first causal evidence linking meal timing and increased weight gain.

"How or why a person gains weight is very complicated, but it clearly is not just calories in and calories out," said Fred Turek, professor of neurobiology and physiology in the Weinberg College of Arts and Sciences and director of the Center for Sleep and Circadian Biology. "We think some factors are under circadian control. Better timing of meals, which would require a change in behavior, could be a critical element in slowing the ever-increasing incidence of obesity."

The findings could have implications for developing strategies to combat obesity in humans, as the United States and the world battle what has been called an "obesity epidemic." More than 300 million adults worldwide are obese, including more than a third of American adults.

Details of the obesity study, which was led by Turek, will be published online Sept. 3 by the journal Obesity.

"One of our research interests is shift workers, who tend to be overweight," said lead author Deanna M. Arble, a doctoral student in Turek's lab. "Their schedules force them to eat at times that conflict with their natural body rhythms. This was one piece of evidence that got us thinking -- eating at the wrong time of day might be contributing to weight gain. So we started our investigation with this experiment."

Simply modifying the time of feeding alone can greatly affect body weight, the researchers found. Mice that were fed a high-fat diet during normal sleeping hours gained significantly more weight (a 48 percent weight increase over their baseline) than mice eating the same type and amount of food during naturally wakeful hours (a 20 percent increase over their baseline). There was no statistical difference between the two groups regarding caloric intake or the amount of activity.

Over a period of six weeks, both groups of mice were allowed to eat as much high-fat diet as they wanted during their daily 12-hour feeding phase. (Much like many humans, mice have a preference for high-fat food.) Since mice are nocturnal, the 12-hour feeding phase was during the day for those fed during normal sleeping hours and during the night for those fed during naturally wakeful hours. Food was not provided during the other 12 hours of their day.

Our circadian clock, or biological timing system, governs our daily cycles of feeding, activity and sleep, with respect to external dark and light cycles. Recent studies have found the body's internal clock also regulates energy use, suggesting the timing of meals may matter in the balance between caloric intake and expenditure.

The researchers next plan to investigate the molecular mechanisms behind their observation that eating at the "wrong" time can lead to weight gain.

In addition to Turek and Arble, other authors of the paper are Joseph Bass, Aaron D. Laposky and Martha H. Vitaterna, all from Northwestern.

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Goodbye Needle, Hello Smoothie: New Generation Oral Vaccine Uses Dairy Probiotics To Protect Against Disease

Goodbye Needle, Hello Smoothie: New Generation Oral Vaccine Uses Dairy Probiotics To Protect Against Disease

  1:55:00 AM    Science Lover

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The dendritic cell (green) engulfs the lactobacilli (small blue dots),
which release the vaccine. The dendritic cells will induce the
proliferation and the activation of T and B cells which will
eliminate the infected cells. (Credit: Mansour Mohamadzadeh)

Instead of a dreaded injection with a needle, someday getting vaccinated against disease may be as pleasant as drinking a yogurt smoothie.

A researcher from the Northwestern University Feinberg School of Medicine has developed a new oral vaccine using probiotics, the healthy bacteria that are found in dairy products like yogurt and cheese. He has successfully used the approach in a preclinical study to create immunity to anthrax exposure. He also is using the method to develop a breast cancer vaccine and vaccines for various infectious diseases.

This new generation vaccine has big benefits beyond eliminating the "Ouch!" factor. Delivering the vaccine to the gut -- rather than injecting it into a muscle -- harnesses the full power of the body's primary immune force, which is located in the small intestine.

"This is potentially a great advance in the way we give vaccines to people," said Mansour Mohamadzadeh, the lead author and an associate professor of medicine in gastroenterology at the Feinberg School.

"You swallow the vaccine, and the bacteria colonize your intestine and start to produce the vaccine in your gut," Mohamadzadeh said. "Then it's quickly dispatched throughout your body. If you can activate the immune system in your gut, you get a much more powerful immune response than by injecting it. The pathogenic bacteria will be eliminated faster."

Most vaccines consist of protein and won't maintain their effectiveness after being digested by the stomach. However, the lactobacillus protects the vaccine until it is in the small intestine.

The Northwestern study was reported in a recent issue of the Proceedings of the National Academy of Science.

There are other advantages to the new oral vaccine. Probiotics, which are natural immune stimulators, eliminate the need for a chemical in traditional vaccines that inflames the immune system and triggers a local immune response. The chemical, called an adjuant, may cause side effects such as dizziness, arm swelling and vomiting. Probiotic vaccines also are inexpensive to produce.

The specially engineered vaccine gives more immune bang for the buck than an injected one because it induces a local and a systemic immune response. The vaccine targets the first line of gut immune cells called dendritic cells -- the commanders-in-chiefs of the immune system.

They engulf the vaccine then instruct the immune system's foot soldiers -- killer T-cells and B-cells -- to seek out and destroy any cells in the body infected with a particular bacterium or virus.

In the study, Mohamadzadeh fed mice the new oral anthrax vaccine, and then exposed them to anthrax bacteria. Eighty percent of the mice survived, which is comparable to the results when mice were injected with anthrax vaccine, he said.

"Their immune response was higher and more robust than with the injected vaccine," Mohamadzadeh said. The mice generated a much higher T and B immunity against the pathogenic bacteria.

Mohamadzadeh's vaccine technology can be applied to many other diseases. He is developing an oral vaccine for breast cancer using probiotics. The vaccine would use the Her2/neu breast cancer antigen, a protein highly produced by breast tumor cells, and train the immune system to destroy any cells producing Her2/neu, he said.

In addition, Mohamadzadeh has developed a "multi-tasking" cancer vaccine against breast, colon and pancreatic cancer that soon will be tested in mouse models.

The technology also can be used to develop a probiotic vaccine for HIV, hepatitis C and the flu, he said.

Terrence Barrrett, M.D., chief and professor of gastroenterology at the Feinberg School, said delivering a vaccine to the gut is the most logical route.

"Nature isn't used to seeing antigens injected into a muscle," said Barrett, who also is a physician at Northwestern Memorial Hospital. "The place where your immune system is designed to encounter and mount a defense against antigens is your gut."

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Journal reference:

1. M. Mohamadzadeh, T. Duong, S. J. Sandwick, T. Hoover, and T. R. Klaenhammer. Dendritic cell targeting of Bacillus anthracis protective antigen expressed by Lactobacillus acidophilus protects mice from lethal challenge. Proceedings of the National Academy of Sciences, 2009; DOI: 10.1073/pnas.0900029106

Adapted from materials provided by Northwestern University.

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