SCIENCE & TECHNOLOGY CONCENTRATES
Miniature rockets zooming through a person’s body are still the stuff of science fiction. With the goal of using the devices to deliver drugs, researchers have built some versions in the lab, but the tiny moPoly(methyl methacrylate) coating tors typically propel themselves with toxic fuels such as hydrogen Ethanol peroxide, or they emit harmful metals such as gallium in their Formaldehyde exhaust. A team led by Ayusman Sen of Pennsylvania State PECA-infused bead Sodium cyanoacrylate University recently developed a Salt solution micromotor that carries its own fuel: a polymer approved by the Food & Drug Administration for A micromotor zooms around because of the surface tension gradient created when its biomedical applications. And the polymer fuel breaks down. tiny racer expels low levels of ethanol and formaldehyde, which are naturally occurring compounds found in food and drink (J. Am. Chem. Soc. 2013, DOI: 10.1021/ja4089549). To make the VIDEO ONLINE motor, the researchers soaked a 300-µm-diameter anion-exchange bead in the fuel, poly(2-ethyl cyanoacrylate) (PECA). Then, they coated half of the bead with an inert compound, poly(methyl methacrylate), to give the motor directionality. When floated atop a high-concentration salt solution, the bead releases hydroxide ions from its uncoated half. The ions break down PECA, releasing ethanol, formaldehyde, and cyanoacrylate monomer. These compounds, the researchers believe, create a surface tension gradient around the motor that propels it forward at some 500 body lengths per second.—LKW ADAPTED FROM J. AM. CHEM. SOC.
SCIENCE
The structure of silica glass has been something of a mystery to scientists. Because of the disordered, amorphous nature of the material, researchers can’t construct a picture of its atoms by using X-ray crystallography as they can with bulk crystals. Instead, an international team led by David A. Muller of Cornell University and Ute Kaiser of Germany’s University of Ulm devised a high-resolution transmission electron microscopy (TEM) method to get an atomicscale glimpse of this material in motion and used it to study sheets of glass just two atoms thick (Science 2013, DOI: 10.1126/ science.1242248). With that technique, the researchFalse-colored ers recorded imTEM image shows ages of the glass as solid (yellow) and it deformed upon molten (blue) silica changing from solid glass, with actively to liquid. The TEM rearranging atoms images and video in between (red). Each ring of atoms is reveal “a complex about 1 nm across. dance” of silicon and oxygen atoms, according to the team. Ring structures open and close. Atoms swap places. The results will likely help scientists create a better picture of the atom dynamics in amorphous materials, which are ubiquitous. Silica glass, for example, can be found in semiconductors and optical fibers.—BH
MICROMOTOR USES BIOCOMPATIBLE FUEL
they first suspend the bacteria in gelatin mixed with a photosensitive molecule that promotes cross-linking between polypeptides in the gelatin. Next, they use multiphoton excitation with 740-nm light to initiate the cross-linking and create containers around the bacteria in a variety of configuPROC. NATL. ACAD. SCI. USA
A GLIMPSE OF SILICA IN MOTION
ARRANGING BACTERIA IN 3-D Bacteria live in a three-dimensional environment, but scientists don’t have a good way to define the shape of environments in the lab. To achieve that control, Jason B. Shear and coworkers at the University of Texas, Austin, use multiphoton lithography, a 3-D printing technique, to sculpt the bacterial environment into a variety of 3-D shapes (Proc. Natl. Acad. Sci. USA 2013, DOI: 10.1073/pnas.1309729110). In this method,
In this false-colored fluorescence image, S. aureus (blue) is surrounded on all sides by P. aeruginosa (green), which shares its antibiotic resistance. The gelatin is in red. CEN.ACS.ORG
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rations—adjacent, nested, or free-floating. Finally, they culture the bacteria inside the containers until they reach the desired density. Although the bacteria are fully enclosed, the porous gelatin easily transmits biologically active molecules, such as those required for bacterial signaling. In a model system, naturally susceptible Staphylococcus aureus display resistance to the β-lactam ampicillin when they are nested within a layer of Pseudomonas aeruginosa, which produce enzymes that degrade β-lactams, the researchers report.—CHA
SHORING UP DRUG LINKAGES Two antibody-drug conjugates are on the market today, and both of those targeted cancer therapies involve a maleimide, a moiety that readily reacts with thiols. Maleimide linkages aren’t always desirable because they can break apart and recombine
SCIENCE & TECHNOLOGY CONCENTRATES
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COURTESY OF SHIGEHIRO ASANO
Conceptual drawing of a protein conjugate made with a methylsulfonylphenyloxadiazole.
with reactive groups in other biomolecules in the body. A team at Scripps Research Institute, La Jolla, Calif., now reports compounds—methylsulfonylphenyloxadiazoles—that complement maleimides by producing a more stable protein-drug linkage (Angew. Chem. Int. Ed. 2013, DOI: 10.1002/anie.201306241). Narihiro Toda, Shigehiro Asano, and Carlos F. Barbas III took inspiration from a heterocyclic reagent that selectively blocks protein thiols. They synthesized a family of similar molecules and, working at physiological pH, determined that methylsulfonylphenyloxadiazoles are selective for cysteine thiols over other reactive moieties in proteins. They made protein conjugates with methylsulfonylphenyloxadiazoles and found that the conjugates were more stable than the corresponding maleimides in human plasma. Researchers’ excitement about drug conjugates has led to several reports of new linkers. The Barbas team adds a brandnew approach that researchers should keep in mind, says Peter D. Senter, vice president of chemistry at the antibody-drug conjugate firm Seattle Genetics. Sigma-Aldrich is commercializing the technology.—CD
QUASICRYSTALLINE OXIDES Two years after the 2011 Nobel Prize in Chemistry was awarded for the discovery of quasicrystals, this class of unusually ordered materials remains relatively obscure. Unlike conventional crystals, quasicrystals lack periodicity, meaning their atomic structures do not repeat in three dimensions at fixed intervals. Most quasicrystals, some of which are used to harden steel and endow high-end cookware with stick- and scratch-resistance, are metals and are prepared via a small number of alloying methods. Stefan Förster, Wolf Widdra, and coworkers at Martin Luther University of Halle-Wittenberg, in Germany, have demonstrated a new way to
make quasicrystals and used the method to make a quasicrystalline oxide film (Nature 2013, DOI: 10.1038/nature12514). After growing a crystalline film of BaTiO3 on platinum via conventional methods, the team heated the material in vacuum. On the basis of electron diffraction and microscopy analysis, they conclude that the heat treatment and BaTiO3/platinum interfacial energy drive the oxide to adopt a quasicrystalline structure. The method, which had not been expected to yield oxide quasicrystals, might lead to other oxide quasicrystals with unexpected properties, Widdra says.—MJ
TWO DRUGS CAN BE BETTER THAN ONE Two drugs can be better than one when one counteracts the other’s side effects. A recent study shows a way to predict molecular interactions that make this possible. Ravi Iyengar of Icahn School of Medicine at Mount Sinai and coworkers also determined that side effects of tens of thousands of other drugs might be mitigated in a similar way (Sci. Transl. Med. 2013, DOI: 10.1126/sci translmed.3006548). Their work suggests that this is a strategy drug companies might want to pursue. The researchers probed FDA’s publicly accessible database of adverse drug interactions to find drugs that might reduce the relatively high incidence of heart attacks in patients taking GlaxoSmithKline’s diabetes drug rosiglitazone. The search revealed that patients who take both rosiglitazone and another diabetes drug, Amylin Pharmaceuticals’ exenatide, experienced H2N significantly fewer heart attacks than other rosiglitazone users. Computational modeling enabled the team to predict the biomolecular target interaction that enables exenatide to exert its mitigating effect, and they confirmed that mechanism in mouse studies. Further analysis by the group showed that more than 19,000 other drug combinations might be similarly beneficial.—SB
EVIDENCE OF WATER NEAR DEAD STAR Astronomers have found extrasolar rocky bodies that could harbor water, but until now, chemical evidence of water’s presence has been lacking. Analysis of rocky debris surrounding a burned-out star has CEN.ACS.ORG
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provided that evidence (Science 2013, DOI: 10.1126/science.1239447). The disk of debris around the white dwarf GD 61 contains remnants of a planetlike body ripped apart by the star’s gravity. From an estimate of oxygen’s abundance in the debris, researchers can infer water’s presence. Astronomer Jay Farihi of the University of Cambridge and coworkers measured oxygen’s and other elements’ spectral lines emanating from the vicinity of GD 61 with the Hubble Space Telescope and instruments at the W. M. Keck Observatory, in Hawaii. Plugging these data into white dwarf atmosphere models yielded elemental abundances. Carbon and metals, which react with oxygen to form CO2 and metal oxides, were present, the researchers found, but not at high enough levels to account for oxygen’s abundance. The remaining oxygen likely exists in water, the researchers conclude. The findings suggest that rocky bodies can retain water after stars like the sun swell into red giants and then burn out, forming white dwarfs.—PK
ACCELERATING DIABETIC WOUND HEALING Each year, tens of thousands of people with diabetes in the U.S. have a lower limb amputated because a foot wound failed to heal. Identification of an enzyme that interferes with healing in diabetes patients may help prevent these amputations. Mayland Chang of the University of Notre Dame and colleagues looked for matrix O metalloproteinases (MMPs) in S S the wounds of O O healthy and diabetic mice. The MMP-9 inhibitor enzymes remodel the extracellular matrix in tissue during wound healing. The scientists used micrometersized polymer beads decorated with an inhibitor to snag active enzymes in the wounds. They detected active MMP-9 in both normal and diabetic tissue but found that levels of MMP-9 were almost two times as high in diabetic wounds as in normal ones, suggesting that MMP-9 is a roadblock to swift healing (ACS Chem. Biol. 2013, DOI: 10.1021/cb4005468). They treated wounds in diabetic mice with an inhibitor of MMP9 and found that the wounds were 92% healed after 14 days, compared with 74% wound closure in untreated mice. The finding suggests that enzyme inhibition could be a wound treatment strategy.—JNC
