SENSING THE SCENT OF DEATH G protein-coupled receptors (GPCRs) play important roles in cellular responses. Trace-amine-associated receptors (TAARs) are a class of GCPR that bind to biogenic amines. One traceamine-associated receptor, known as TAAR13c, functions as an olfactory receptor highly specific for cadaverine, a deathassociated odor. Generated by the bacterial carboxylation of lysine, this odor is a marker not just for cadavers but also for decayed foods. Thus, having a detector for cadaverine could be useful for industrial uses, scientific investigations, and other applications. Yang et al. (DOI: 10.1021/acsnano.7b04992) created a cadaverine sensor by reconstituting TAAR13c receptors in nanodiscs, which were then immobilized on floating electrodes of a carbon nanotube field-effect transistor (CNT-FET) in an orientation that optimized the number of exposed binding sites. The researchers used E. coli to produce the receptors, which were then fashioned into nanodiscs. These nanodiscs were arranged onto floating electrodes using the half V5 antibody as a linker, with the receptor’s binding pocket on the exposed side. After exposing various concentrations of cadaverine to this device, the researchers monitored drain-source currents. These tests showed that conductance sharply increased with concentrations as low as 10 pM of cadaverine, significantly lower than the tolerance of cadaverine in various foods. These results suggest that this device could be used to assess food quality and has a sensitivity even higher than those of cells or biological systems. The researchers demonstrated this proof-of-principle by testing this device on samples of salmon, beef, and pork fat. They suggest that their bioelectric nose could also be a useful tool for detecting corpses for disaster responses.
Marcus et al. (DOI: 10.1021/acsnano.7b05044) measured mechanical properties of polished sections of the beak of a steelhead parrotfish (Chlorurus microrhinos), then performed additional structural and chemical analysis using scanning electron microscope energy dispersive X-ray analysis, electron probe microanalysis, micro-Raman spectroscopy, photoelectron emission microscopy with polarization-dependent imaging contrast, and X-ray microdiffraction. Nanoindentation tests revealed stiffness in the biting direction among the highest of any biomineral measured. The enameloid composing these teeth, made of fluorapatite (Ca5(PO4)3F), consists of 100 nm wide, microns-long crystals that are co-oriented and assembled into bundles that are interwoven like the warp and the weave in fabric. These “fibers” decrease in average diameter from 5 μm at the base to 2 μm at the tip, with hardness increasing with smaller fiber size. The authors suggest that this material could serve as an inspiration for tough and wear-resistant ceramic-based composites.
AN OPTOGENETICS BLUE LIGHT SPECIAL Over the past several years, a growing body of research has explored the use of optogenetic manipulation to provide spatiotemporally precise control over molecular processes, cellular signals, and animal behavior. Thus far, the majority of genetically encoded photoreceptors used for this technique can only be activated by visible light. Because the epidermis is relatively impervious to visible light, many studies have relied on surgically implanting light-emitting diodes in vivo, which inevitably damages healthy tissue and still has poor penetration. To avoid these consequences, some researchers have explored the use of photosensitive proteins that react to near-infrared light, which penetrates deeper into tissues; however, these proteins are relatively inefficient for optogenetic manipulation compared to those that use visible light. Seeking an alternative, Zheng et al. (DOI: 10.1021/ acsnano.7b06395) looked to rare-earth upconversion nanoparticles, which can convert near-infrared light to visible light. The researchers created lanthanide-doped nanoparticles capable of converting near-infrared light to blue light. They then attached plasmids on the surface of these nanoparticles for the Arabidopsis flavoprotein cryptochrome 2 and its interacting partner Cib1, which can express a blue light photoreceptor. In vitro experiments showed that this system could generate photoreceptors in cells that responded to stimulation by near-infrared light, even through pig skin. Linking this system to an apoptotic pathway, the researchers showed that it could be used to trigger cell death both in vitro and in vivo in a mouse tumor model. The authors suggest that this system could be used to overcome the
WHAT GIVES PARROTFISH THEIR BITE? Parrotfish, a diverse family of fish found in the tropics and subtropics, bite corals to eat their polyps and symbionts. The ground-up coral skeletons that they excrete contribute significantly to the white sand beaches characteristic of tropical islands. These fishes’ biting beaks are composed of two upper dental plates and two lower ones, each composed of about 15 rows of teeth that continuously form, becoming more mineralized and rigid over time as they mature and move toward the biting end of the beak. The mature teeth that make contact with corals can withstand enormous contact stresses, but the microscopic properties that imbue them with this quality have not been known. © 2017 American Chemical Society
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Published: December 26, 2017 11758
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MAKING IT GEL WITH MEMBRANE-COATED NANOPARTICLES Colloidal gels, made of networks of particles that interact through electrostatic charge interactions, have gained increasing attention for their many varied potential applications. In particular, composing these materials out of therapeutic nanoparticles makes them suitable for drug delivery, tissue engineering, and other biomedical applications. One emerging way to biofunctionalize synthetic nanoparticles for these uses is to coat them with natural cell membranes. These membranes tend to have negative surface charge, regardless of their source, which enables them to interact with cationic materials without the need for further modification. Taking advantage of this quality, Zhang et al. (DOI: 10.1021/ acsnano.7b06968) used cell-membrane-coated polymeric nanoparticles to create colloidal gels with therapeutic properties. The researchers wrapped red blood cell (RBC) membranes around cores composed of poly(lacto-co-glycolic acid) (PLGA), which carried a negative surface charge. They mixed these with chitosan-functionalized PLGA nanoparticles, which had positive surface charge. Together, these two oppositely charged nanoparticles self-assembled into a colloidal gel. Tests showed that this gel demonstrated shear-thinning behavior when an external shear force was applied, but recovered its strong cohesive properties upon removal. Additional experiments using group A Streptococcus (GAS) and its toxin, Streptolysin-O, showed that this gel inhibited toxin-induced hemolysis in vitro like RBC membrane-wrapped nanoparticles alone. In addition, in mouse models of GAS infection, the gel showed significant therapeutic efficacy, warding off bacterial skin lesion development. The authors suggest that this colloidal gel system could have promise for a variety of therapeutic applications.
drawbacks of current optogenetic systems and could potentially serve as a therapeutic modality.
BOOSTING THE RELIABILITY OF THERMAL SCANNING PROBE LITHOGRAPHY Scanning probe lithography (SPL) has been used for fabricating semiconductor nanoscale devices, chemically activating polymer surfaces to create protein gradients, and patterning 10 nm wide chemical guiding patterns for block copolymers. Thermal SPL (tSPL), which uses a heated scanning probe, has demonstrated overlay accuracies better than 5 nm and the capability to fabricate three-dimensional depth profiles with nanometer-scale accuracy. The resolution of t-SPL is highest for shallow patterns due to the conical shape of the tip. But for nanoscale patterns, little is known about the mechanisms controlling pattern formation and how to optimize resolution. To explore this topic, Cho et al. (DOI: 10.1021/ acsnano.7b06307) evaluated the t-SPL parameters that influence high-resolution patterning on the polyphthalaldehyde (PPA) layer of a pattern transfer stack. The researchers found that the best pattern geometries are obtained at a tip temperature of ∼600 °C, which is below or close to the transition from mechanical indentation to thermal evaporation. At this temperature, plastic deformation of the resist leads to a reduction of the pattern depth at tight pitch, limiting the achievable resolution. Still, the researchers show that by optimizing pattern conditions, this technique could achieve 11 nm half-pitch dense lines in a HM8006 transfer layer and 14 nm half-pitch dense lines and Llines in silicon. For silicon, the line edge roughness measured 2.6 nm, and the feature size measured 7 nm. The authors suggest that being able to fabricate such small features without proximity corrections in a controlled and reproducible manner has exciting potential for nanoscale device fabrication.
INTERFACING DNAZYME NANODEVICES WITH ENZYMES Researchers have explored DNA nanodevicescomputational assemblers that switch defined states upon external stimulationas components for cellular monitor systems and smart therapeutic tools. However, interfacing these artificial devices with natural molecular machineries in living cells has been challenging. Thus far, cellular DNA nanodevices that work as biosensors have been designed to respond to ions, pH, and small molecules. However, nanodevices that respond to biomacromolecules such as enzymes remain relatively unexplored, even though enzymes are critical in numerous biological processes and play important roles in many diseases. Working toward this goal, Chen et al. (DOI: 10.1021/ acsnano.7b06728) developed a generic method for programming the assembly of enzyme-initiated DNAzyme nanodevices 11759
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into capsids under high pressure. The authors suggest that this method could be translated to modify other nonsuitable pores to insert into lipid bilayer membranes.
(DzNanos) in living cells. The researchers designed two assembly programs for these devices: one method induced split assembly of two partzymes and the other used toehold exchange displacement assembly of one intact DNAzyme; both programs used telomerase as a model enzyme. These programs used MnO2 nanosheets as both DNA carriers and as a source of Mn2+ as the DNAzyme cofactor. Tests showed that the intact DNAzyme obtained a higher assembly yield and better catalytic performance, which the researchers ascribed to proper conformational folding and active misplaced assembly. This DzNano operated autonomously in living cells with high cleavage capacity. The authors suggest that this scheme could be used to induce the assembly of other DzNanos using different enzymes, with applications for monitoring enzyme catalysis in situ as well as implementing cellular modulations, behaviors, and pathways for diagnostic and therapeutic applications.
THE RACE TOWARD HIGH-TEMPERATURE SUPERCONDUCTIVITY HEATS UP Carbon-based strongly bonded materials have become a growing focus of research efforts for their potential for high-temperature superconductivity. To achieve high superconducting transition temperatures (Tc), research suggests that these materials must have carbon in an sp3 or sp2 state, doped with appropriate dopants to provide free carriers. Thus, much work in this area has focused on doped diamond, nanotubes, and buckyballs. However, the highest reported Tc of these materials was only 33 K. In bulk materials, the highest reported Tc of boron-doped diamond was 11 K with 5% at B concentration. While higher concentrations of B could increase Tc, boosting B has proven challenging. Bhaumik et al. (DOI: 10.1021/acsnano.7b06888) accomplish this feat by boosting Tc in bulk carbon-based materials. The researchers formed B-doped Q-carbon by nanosecond laser melting of B/C multilayered films in a super undercooled state, followed by rapid quenching, resulting in 27% B doping. Electron energy loss spectroscopy analysis and Raman spectroscopy both showed that ∼67% of the total boron exists with carbon in a sp3 hybridized state. This factor appears to be responsible for the high Tc = 55 K. By studying vibrational modes, the researchers suggest that a higher density of states near the Fermi level and moderate-to-strong electron−phonon coupling lead to this high Tc. They add that finding ways to increase boron content further could lead to an even higher Tc, coming ever closer to the ultimate goal of room-temperature superconductivity.
INSERTING NANOPORES INTO BILAYER MEMBRANES: THE HOLE STORY Pore-forming biological macromolecules have attracted increasing attention for a variety of applications, including indirect DNA sequencing, molecular sensing, and protein characterization. For these uses, a single biological nanopore is typically inserted into a membrane that separates two electrolyte compartments. When a voltage bias is applied between the two compartments, it generates a steady-state ionic current that reports on ion flow through the pore. The vast majority of biological pores studied thus far insert easily into lipid bilayer membranes. Although other biological pores might be better performers, these have largely remained unexplored due to their inability to be stably placed into lipid bilayers. To increase the number of suitable biological pores, Cressiot et al. (DOI: 10.1021/acsnano.7b06980) developed a way to modify pore-forming macromolecules to insert them into lipid bilayer membranes. As a model biological pore, the researchers used the portal protein from a thermophilic bacteriophage G20c. The researchers genetically modified the natural protein, which is shaped like a champagne cork composed of 12 monomers with a central hole down the center, by adding amino acids to increase the pore diameter and introducing a cysteine mutation near the cap−stem junction. To these cysteines, the researchers conjugated a maleimide-porphyrin derivative to insert this pore into a lipid bilayer. Using three different cyclodextrins of varying sizes, the researchers probed the modified pore’s interior size and shape, revealing an asymmetric transport mechanism that may originate from the portal’s original function in inserting DNA 11760
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A TWIST ON SUPRAMOLECULAR HELICITY Helical chirality of nanoscale architectures in polymer and supramolecular self-assembly systems plays an important role in biomedical applications, chiroptical switches, asymmetric catalysis, and optoelectronics. Thus far, numerous helical assemblies of either handedness have been obtained by selfassembly of chiral or achiral small molecular building blocks. However, how achiral factors affect the chirality of these supramolecular assemblies remains unclear. The mechanism behind the twisting tendency and handedness development from building blocks is not well understood, and it still remains a challenge to control helicity or invert chirality of these nanostructures during self-assembly. To explore these questions, Liu et al. (DOI: 10.1021/ acsnano.7b06097) studied macroscopic chirality and dynamic manipulation of chiroptical activity of four self-assembled chiral hydrogels and their helical opposites. Each of these hydrogels has chiral phenylalanine derivatives at the center, with achiral carboxylic acid groups terminating the phenylalanine arms. The researchers exchanged these carboxylic acid groups with oligo(ethylene glycol), then observed the results with scanning electron microscopy, circular dichroism, crystallography, and molecular dynamics calculations. These analytic methods showed that this exchange inverted the handedness of each of these molecules. Further investigation suggested that this inversion was induced by distinctive stacking modes. The authors suggest that this simple switch could be used to achieve handedness inversion in other supramolecular systems, not only as a way to study the chiral self-assembly process in supramolecular chemistry but also to develop smart materials with controllable handedness.
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