Friday, January 13, 2012

Nanotechnology: The art of molecular carpet-weaving

 Stable two-dimensional networks of organic molecules are important components in various nanotechnology processes. However, producing these networks, which are only one atom thick, in high quality and with the greatest possible stability currently still poses a great challenge. Scientists from the Excellence Cluster Nanosystems Initiative Munich (NIM) have now successfully created just such networks made of boron acid molecules. The current issue of the scientific journal ACSnano reports on their results.

Even the costliest oriental carpets have small mistakes. It is said that pious carpet-weavers deliberately include tiny mistakes in their fine carpets, because only God has the right to be immaculate. Molecular carpets, as the nanotechnology industry would like to have them are as yet in no danger of offending the gods. A team of physicists headed by Dr. Markus Lackinger from the Technische Universität München (TUM) und Professor Thomas Bein from the Ludwig-Maximilians-Universität München (LMU) has now developed a process by which they can build up high-quality polymer networks using boron acid components.

The "carpets" that the physicists are working on in their laboratory in the Deutsches Museum München consist of ordered two-dimensional structures created by self-organized boron acid molecules on a graphite surface. By eliminating water, the molecules bond together in a one-atom thick network held together solely by chemical bonds -- a fact that makes this network very stable. The regular honey-comb-like arrangement of the molecules results in a nano-structured surface whose pores can be used, for instance, as stable forms for the production of metal nano-particles.

The molecular carpets also come in nearly perfect models; however, these are not very stable, unfortunately. In these models the bonds between the molecules are very weak -- for instance hydrogen bridge bonds or van der Waals forces. The advantage of this variant is that faults in the regular structure are repaired during the self-organization process -- bad bonds are dissolved so that proper bonds can form.

However, many applications call for molecular networks that are mechanically, thermally and/or chemically stable. Linking the molecules by means of strong chemical bonds can create such durable molecule carpets. The down side is that the unavoidable weaving mistakes can no longer be corrected due to the great bonding strength.

Markus Lackinger and his colleagues have now found a way to create a molecular carpet with stable covalent bonds without significant weaving mistakes. The method is based on a bonding reaction that creates a molecular carpet out of individual boron acid molecules. It is a condensation reaction in which water molecules are released. If bonding takes place at temperatures of a little over 100°C with only a small amount of water present, mistakes can be corrected during weaving. The result is the sought after magic carpet: molecules in a stable and well-ordered one-layer structure.

Markus Lackinger's laboratory is located in the Deutsches Museum München. There he is doing research at the Chair of Prof. Wolfgang Heckl (TUM School of Education, TU München). Prof. Bein holds a Chair at the Department of Chemistry at the LMU. The research was conducted in collaboration with Prof. Paul Knochel's work group (LMU) and Physical Electronics GmbH, with funding by the Excellence Cluster Nanosystems Initiative Munich (NIM) and the Bavarian Research Foundation (BFS).

Story Source:

The above story is reprinted from materials provided by Technische Universitaet Muenchen.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

Journal Reference:

Jürgen F. Dienstmaier, Alexander M. Gigler, Andreas J. Goetz, Paul Knochel, Thomas Bein, Andrey Lyapin, Stefan Reichlmaier, Wolfgang M. Heckl, Markus Lackinger. Synthesis of Well-Ordered COF Monolayers: Surface Growth of Nanocrystalline PrecursorsversusDirect On-Surface Polycondensation. ACS Nano, 2011; 5 (12): 9737 DOI: 10.1021/nn2032616

Silk microneedles deliver controlled-release drugs painlessly

The research paper "Fabrication of Silk Microneedles for Controlled-Release Drug Delivery" appeared in December 2 online in advance of print.

The Tufts researchers successfully demonstrated the ability of the silk microneedles to deliver a large-molecule, enzymatic model drug, horseradish peroxidase (HRP), at controlled rates while maintaining . In addition, silk microneedles loaded with tetracycline were found to inhibit the growth of , demonstrating the potential of the microneedles to prevent local infections while also delivering therapeutics.

"By adjusting the post-processing conditions of the silk protein and varying the drying time of the silk protein, we were able to precisely control the drug release rates in laboratory experiments," said Fiorenzo Omenetto, Ph.D., senior author on the paper. "The new system addresses long-standing drug delivery challenges, and we believe that the technology could also be applied to other biological ."

The Drug Delivery Dilemma

While some drugs can be swallowed, others can't survive the . Hypodermic injections can be painful and don't allow a slow release of medication. Only a limited number of small-molecule drugs can be transmitted through transdermal patches. Microneedles—no more than a micron in size and able to penetrate the upper layer of the skin without reaching nerves—are emerging as a painless new drug delivery mechanism. But their development has been limited by constraints ranging from harsh manufacturing requirements that destroy sensitive biochemicals, to the inability to precisely control drug release or deliver sufficient drug volume, to problems with infections due to the small skin punctures.

The process developed by the Tufts bioengineers addresses all of these limitations. The process involves ambient pressure and temperature and aqueous processing. Aluminum microneedle molding masters were fabricated into needle arrays of about 500 µm needle height and tip radii of less than 10 µm. The elastomer polydimethylsiloxane (PDMS) was cast over the master to create a negative mold; a drug-loaded silk protein solution was then cast over the mold. When the silk was dry, the drug-impregnated silk microneedles were removed. Further processing through water vapor annealing and various temperature, mechanical and electronic exposures provided control over the diffusity of the silk microneedles and drug release kinetics.

"Changing the structure of the secondary enables us to 'pre-program' the properties of the with great precision," said David L. Kaplan, Ph.D., coauthor of the study, chair of biomedical engineering at Tufts and a leading researcher on silk and other novel biomaterials. "This is a very flexible technology that can be scaled up or down, shipped and stored without refrigeration and administered as easily as a patch or bandage. We believe the potential is enormous."

More information: Tsioris, K., Raja, W. K., Pritchard, E. M., Panilaitis, B., Kaplan, D. L. and Omenetto, F. G. (2011), Fabrication of Silk Microneedles for Controlled-Release Drug Delivery. Advanced Functional Materials. doi: 10.1002/adfm.201102012

Provided by Tufts University

Scientists pioneer new method for watching proteins fold

The research was conducted by Feng Gai, professor in the Department of Chemistry in the School of Arts and Sciences, along with graduate students Arnaldo Serrano, also of Chemistry, and Robert Culik of the Department of Biochemistry and Molecular Biophysics at Penn’s Perelman School of Medicine. They collaborated with Michelle R. Bunagan of the College of New Jersey’s Department of Chemistry.

Their research was published in the international edition of the journal Angewandte Chemie, where it was featured on the cover and bestowed VIP (very important paper) status.

“One of the reasons that figuring out what happens when proteins fold is difficult is that we don’t have the equivalent of a high-speed camera that can capture the process, “ Gai said.  “If the process were slow, we could take multiple ‘pictures’ over time and see the mechanism at work. Unfortunately, no one has this capability; the folding occurs faster than the blink of an eye.”  

Gai’s team uses infrared spectroscopy — a technique that measures how much light different parts of a molecule absorbs — to analyze proteins’ structure and how this changes. In this case, the researchers looked at a model protein known as Trp-cage with an infrared laser setup.

In this experiment, Gai’s team used two lasers to study structural changes as a function of time. The first laser acts as the starting gun; by heating the molecule, it causes its structure to change. The second laser acts as the camera, following the motions of the protein’s constituent amino acids.
“The protein is made of different groups of atoms, and the different groups can be thought of as springs,” Gai said. “Each spring has a different frequency with which it moves back and forth, which is based on the mass of the atom on either end. If the mass is bigger, the spring oscillates slower. Our ‘camera’ can detect the speed of that motion and we can relate it to the atoms it is made of and how that segment of the protein chain moves.” 

Even in a simple protein like Trp-cage, however, there are many identical bonds, and the researchers need to be able to distinguish one from another in order to see which of them are moving while the protein folds. One strategy they used to get around this problem was to employ the molecular equivalent of a tracking device. 

“We use an amino acid with a carbon isotope marker,” Culik said. “If it’s incorporated into the protein correctly, we’ll know where it is.”

With a single carbon atom of the Trp-cage slightly heavier than the others, the research team can use its signature to infer the position of the other atoms as they fold. The researchers could then “tune” the frequency of their laser to match different parts of the protein, allowing them to isolate them in their analyses.  

Similar isotopes could be inserted in more complicated molecules, allowing their folds to also be viewed with infrared spectroscopy.  
“This technique enhances our structural resolution. It allows us to see which part is moving,” Gai said. “That would allow us to see exactly how a is misfolding in a disease, for example.”

Provided by University of Pennsylvania (news : web)

Lubricant in metal-on-metal hip implants found to be graphite, not proteins

Researchers from Northwestern University, Rush University Medical Center, Chicago, and the University of Duisburg-Essen Germany found that graphitic carbon is a key element in a lubricating that forms on metal-on-metal hip implants. The lubricant is more similar to the lubrication of a than that of a natural joint.

The study will be published Dec. 23 by the journal Science.

Prosthetic materials for hips, which include metals, polymers and ceramics, have a lifetime typically exceeding 10 years. However, beyond 10 years the failure rate generally increases, particularly in young, active individuals. Physicians would love to see that lifespan increased to 30 to 50 years. Ideally, artificial hips should last the patient's lifetime.

"Metal-on-metal implants can vastly improve people's lives, but it's an imperfect technology," said Laurence D. Marks, a co-author on the paper who led the experimental effort at Northwestern. "Now that we are starting to understand how lubrication of these implants works in the body, we have a target for how to make the devices better."

Marks is a professor of materials science and engineering at Northwestern's McCormick School of Engineering and Applied Science.

The ability to extend the life of implants would have enormous benefits, in terms of both cost and quality of life. More than 450,000 Americans, most with severe arthritis, undergo each year, and the numbers are growing. Many more thousands delay the life-changing surgery until they are older, because of the limitations of current implants.

" is the greatest advancement in the treatment of end-stage arthritis in the last century," said co-author and principal investigator Dr. Joshua J. Jacobs, the William A. Hark, M.D./Susanne G. Swift Professor of Orthopedic Surgery and professor and chair of the department of orthopedic surgery at Rush. "By the time patients get to me, most of them are disabled. Life is unpleasant. They have trouble working, playing with their grandchildren or walking down the street. Our findings will help push the field forward by providing a target to improve the performance of hip replacements. That's very exciting to me."

Earlier research by team members Alfons Fischer at the University of Duisburg-Essen and Markus Wimmer at Rush University Medical Center discovered that a lubricating layer forms on metallic joints as a result of friction. Once formed, the layer reduces friction as well as wear and corrosion. This layer is called a tribological layer and is where the sliding takes place, much like how an ice skate slides not on the ice but on a thin layer of water.

But, until now, researchers did not know what the layer was. (It forms on the surfaces of both the ball and the socket.) It had been assumed that the layer was made of proteins or something similar in the body that got into the joint and adhered to the implant's surfaces.

The interdisciplinary team studied seven implants that were retrieved from patients for a variety of reasons. The researchers used a number of analytical tools, including electron and optical microscopies, to study the tribological layer that formed on the metal parts. (An electron microscope uses electrons instead of light to image materials.)

The electron-energy loss spectra, a method of examining how the atoms are bonded, showed a well-known fingerprint of graphitic carbon. This, together with other evidence, led the researchers to conclude that the layer actually consists primarily of graphitic carbon, a well-established solid lubricant, not the proteins of natural joints.

"This was quite a surprise," Marks said, "but the moment we realized what we had, all of a sudden many things started to make sense."

Metal-on-metal implants have advantages over other types of implants, Jacobs said. They are a lower wear alternative to metal-on-polymer devices, and they allow for larger femoral heads, which can reduce the risk of hip dislocation (one of the more common reasons for additional surgery). Metal-on-metal also is the only current option for a hip resurfacing procedure, a bone-conserving surgical alternative to total hip replacement.

"Knowing that the structure is graphitic carbon really opens up the possibility that we may be able to manipulate the system in a way to produce graphitic surfaces," Fischer said. "We now have a target for how we can improve the performance of these devices."

"Nowadays we can design new alloys to go in racing cars, so we should be able to design for that go into human beings," Marks added.

The next phase, Jacobs said, is to examine the surfaces of retrieved devices and correlate the researchers' observations of the graphitic layer with the reason for removal and the overall performance of the metal surfaces. Marks also hopes to learn how graphitic debris from the implant might affect surrounding cells.

The science of tribology is the study of friction, lubrication and wear. The term comes from the Greek word "tribos," meaning rubbing or sliding.

More information: The Science paper is titled "Graphitic Tribological Layers in Metal-on-Metal Hip Replacements."

Provided by Northwestern University (news : web)