Monday, October 31, 2011

Nanoparticle assembly is like building with LEGOs

New processes that allow nanoparticles to assemble themselves into designer materials could solve some of today's technology challenges, Alex Travesset of Iowa State University and the Ames Laboratory reports in the Oct. 14 issue of the journal Science.

Travesset, an associate professor of physics and astronomy and an associate of the U.S. Department of Energy's Ames Laboratory, writes in the journal's Perspectives section that the controlled self-assembly of nanoparticles could help researchers create new materials with unique electrical, optical, mechanical or transport properties.

"Nanoparticle self-assembly has entered the LEGO era," Travesset said. "You can really work with nanoparticles in the same way you can work with LEGOs. This represents a breakthrough in the way we can manipulate matter. Really revolutionary applications will come."

In his commentary, Travesset reports on the ramifications of a scientific paper also published in the Oct. 14 issue of Science. Lead authors of the scientific paper are Chad Mirkin, director of the International Institute for Nanotechnology at Northwestern University in Evanston, Ill., and George Schatz, a professor of chemistry at Northwestern. Their research team describes new technologies that use complementary DNA strands to link nanoparticles and control how the particles precisely assemble into target structures.

Nanoparticles are so small -- just billionths of a meter -- that it is practically impossible to assemble real materials particle by particle. Past attempts to induce their self-assembly have been successful in only a handful of systems and in very restrictive conditions.

The developments by the Mirkin and Schatz research team are "likely to elevate DNA-programmed self-assembly into a technique for the design of nanoparticle structures a la carte," Travesset wrote.

Travesset's research program includes theoretical studies of the assembly of nanoparticles and how they can be uniformly mixed with polymers. A research paper describing some of his findings was published in the May 27 issue of the journal Physical Review Letters (Dynamics and Statics of DNA-Programmable Nanoparticle Self-Assembly and Crystallization).

With the development of efficient self-assembly technologies, Travesset said there's tremendous potential for nanoparticle science.

"Being able to assemble nanoparticles with such control represents a major accomplishment in our quest to manipulate matter," he wrote in Science. "There are immediate important applications related to catalysis, medical sensing, new optical materials or metamaterials, and others that will follow from these studies.

"Most likely, however, many other applications will arise as we dig deeper, understand better, expand further, and tinker with the opportunities provided by these materials."

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The above story is reprinted (with editorial adaptations ) from materials provided by Iowa State University.

Journal Reference:

Alex Travesset. Self-Assembly Enters the Design Era. Science, 2011; 334 (6053): 183-184 DOI: 10.1126/science.1213070

X-rays help advance the battle against heart disease

Scientists from Imperial College London and Diamond Light Source have revealed the structure of a cholesterol-lowering-drug target. Published in the journal Nature, this finding could lead to much more effective drugs to tackle high cholesterol levels, a condition that increases the risk of heart disease.

The researchers from Imperial College London used intense , generated by the and the European Synchrotron Radiation Facility (ESRF), to determine for the first time the structure of bacterial homologue of the Apical Sodium dependent Bile Acid Transporter (ASBT) protein, a target for drugs since it can affect the level of cholesterol in the blood.

Picture to the right shows a cartoon representation of the ASBTnm structure embedded in the membrane. The protein transports bile acids across the membrane. A bile acid has been trapped in a cavity on the inside face of the protein (shown in wine-red). Energy to drive the transport is provided by . Two sodium ions are bound to the structure and these are shown as pink spheres.

In the liver, cholesterol makes bile acids which are used in the intestine to absorb fat. These bile acids are then reabsorbed by ASBT to be transported to the liver and recycled. It is known that by blocking ASBT, bile returning to the liver are lowered, the liver therefore converts more cholesterol into , which lowers the level of cholesterol in the blood.

“There are currently a number of existing ASBT inhibitors effective in animal models, which were developed without structural knowledge of the protein. Now that we know the shape and size of the drug-binding site within a bacterial model of the protein, this detailed structural information should enable the design of improved drugs which are much more targeted and will “fit” much better.” said Professor So Iwata, David Blow Chair of Biophysics at Imperial College London.

This new knowledge could have a wider impact on drug design. Dr Alexander Cameron from Imperial College London and the Membrane Protein Laboratory at Diamond explains: “As some drugs are poorly absorbed in the intestine or need to be targeted to the liver, ASBT has also received attention as a pro-drug carrier, capable of transporting various compounds coupled to bile acid. This means that there could be scope to improve a number of drugs tackling different problems, for example, cytostatic compounds targeting liver tumours.”

Picture to the left shows a surface representation of ASBTnm looking from the inside face of the membrane showing bile acid bound in a deep cavity.

X-rays help advance the battle against heart disease

ASBT is a membrane protein, one of over 7,000 within the human body, of which many are important drug targets. Over 50% of current commercially available drugs target membrane proteins but they are notoriously hard to crystallise – a step that is a pre-requisite in solving protein structures using a synchrotron. Dr David Drew, Royal Society Research Fellow in the Life Sciences Department at Imperial College London said: “Key to the success was to find a suitable detergent that yielded good crystals, this arduous task was facilitated greatly by a large-scale stability screen we carried out."

The ESRF and Diamond Light Source were essential to screen their crystals and collect the data used to obtain the structure. At Diamond they were also able to access specialised equipment that dehydrates the crystals, improving the resolution of their diffraction data, thus leading to much more accurate results.

“Since membrane proteins are so hard to crystallise, you have to make sure that you try everything possible to improve the quality of data you can extract from each crystal. I am very pleased that the technical effort we have put into this development has resulted in some great scientific results. We will continue to integrate this equipment to help our users with new, challenging projects.” said Dr Juan Sanchez-Weatherby, who played a key role in the development of the crystal dehydration equipment.

More information: ‘Crystal structure of a bacterial homologue of the bile acid sodium symporter ASBT’ Nien-Jen Hu, So Iwata, Alexander D. Cameron, David Drew
DOI: 10.1038/nature10450

Provided by Diamond Light Source

Polymeric material has potential for noninvasive procedures

Scientists at the University of California, San Diego have developed what they believe to be the first polymeric material that is sensitive to biologically benign levels of near infrared (NRI) irradiation, enabling the material to disassemble in a highly controlled fashion. The study represents a significant milestone in the area of light-sensitive material for non-invasive medical and biological applications. Their work is published on line this week in the journal Macromolecules.

"To the best of our knowledge, this is the only polymeric material specifically designed to break down in to small fragments in response to very low levels of NIR ," said Adah Almutairi, PhD, assistant professor at the UCSD Skaggs School of Pharmacy and and director of the Laboratory of Bioresponsive Materials at UC San Diego. "The material was also shown to be well-tolerated in cells before and after irradiation. We think there is great potential for use in human patients, allowing previously inaccessible targets sites to be reached for both treatment and diagnosis."

The properties of so-called "smart" polymeric materials – either synthetic or natural – respond readily to small changes in their environment. They are, therefore, the focus of widespread research to develop tools for such uses as tissue engineering, implants, wound-healing, drug delivery and biosensors.

NIR light can penetrate up to 10 cm into tissue with less damage, absorption and scattering than visible light, and can be remotely applied with high spatial and temporal precision. Most other light-degradable materials that have been developed to date can be difficult to clear from the body, and only a handful of organic materials respond to high-power NIR light. Until now, none were able to respond to low-level, thus safer, NIR light – which causes less photodamage to tissue and cells.

The UC San Diego researchers stated that further studies are warranted to improve the sensitivity of these smart to NIR, and they are currently pursuing several synthetic and engineering strategies to improve design of such biomaterials.

Provided by University of California - San Diego (news : web)

Glucosamine-like supplement suppresses multiple sclerosis attacks

A glucosamine-like dietary supplement suppresses the damaging autoimmune response seen in multiple sclerosis, according to a UC Irvine study.

UCI's Dr. Michael Demetriou, Ani Grigorian and others found that oral N-acetylglucosamine (GlcNAc), which is similar to but more effective than the widely available glucosamine, inhibited the growth and function of abnormal T-cells that in MS incorrectly direct the to attack and break down tissue that insulates nerves.

Study results appear online in The .

Earlier this year, Demetriou and colleagues discovered that environmental and inherited associated with MS – previously poorly understood and not known to be connected – converge to affect how specific sugars are added to proteins regulating the disease.

"This sugar-based supplement corrects a genetic defect that induces cells to attack the body in MS," said Demetriou, associate professor of neurology and microbiology & molecular genetics, "making metabolic therapy a rational approach that differs significantly from currently available treatments."

Virtually all proteins on the surface of cells, including immune cells such as T-cells, are modified by complex sugar molecules of variable sizes and composition. Recent studies have linked changes in these sugars to T-cell hyperactivity and autoimmune disease.

In mouse models of MS-like autoimmune disease, Demetriou and his team found that GlcNAc given orally to those with leg weakness suppressed T-cell hyperactivity and by increasing sugar modifications to the T-cell proteins, thereby reversing the progression to paralysis.

The study comes on the heels of others showing the potential of GlcNAc in humans. One reported that eight of 12 children with treatment-resistant autoimmune inflammatory bowel disease improved significantly after two years of GlcNAc therapy. No serious adverse side effects were noted.

"Together, these findings identify metabolic therapy using dietary supplements such as GlcNAc as a possible treatment for autoimmune diseases," said Demetriou, associate director of UCI's Multiple Sclerosis Research Center. "Excitement about this strategy stems from the novel mechanism for affecting T-cell function and autoimmunity – the targeting of a molecular defect promoting disease – and its availability and simplicity."

He cautioned that more human studies are required to assess the full potential of the approach. GlcNAc supplements are available over the counter and differ from commercially popular . People who purchase GlcNAc should consult with their doctors before use.

Provided by University of California - Irvine