Electronic devices and systems with high stretchability are essential in the fields of wearable electronics, on-skin electronics, soft robotics, and bioelectronics. Stretchable electronic devices conventionally built with elastomeric thin films show a lack of permeability, which not only impedes wearing comfort and creates skin inflammation over long-term wearing, but also limits the design form factors of device integration in the vertical direction. Here we report a new type of stretchable conductor, namely liquid metal fiber mat (LMFM), which is fabricated by simple coating or printing of liquid metal on electrospun elastomeric fiber mat. Liquid metal hanging among the elastomeric fibers self-organizes into the laterally mesh-like and vertically buckled structure, which simultaneously offers high perm eability, stretchability, conductivity, and electrical stability. Besides, LMFM shows smart adaptiveness to omnidirectional stretching over 1800% strain and good biocompatibility. We demonstrate the use of LMFM as the building block to realize highly permeable and multifunctional monolithic stretchable electronics.
The general design of the swinging arm nanostructure complex is shown in Fig. 1a, where a two-enzyme cascade consisting of glucose-6 phosphate dehydrogenase (G6pDH) 19 and malic dehydrogenase (MDH) 20 is displayed on a DNA double-crossover (DX) tile scaffold 21 (DNA sequences for all structures used in this study are shown in Supplementary Figs. S1-S7).G6pDH catalyzes the oxidation of glucose-6-phosphate and the reduction of NAD + to NADH.Subsequently, MDH catalyzes the reduction of oxaloacetate to malic acid using the NADH produced by G6pDH. To facilitate channeling of NADH between G6pDH and MDH, an NAD + -3 functionalized poly(T) 20 oligonucleotide was attached to the DNA tile surface halfway between G6pDH and MDH (see Supplementary Figs. S8-S21 for a detailed description of conjugation, assembly and purification of the nanostructured complex). Fig. 1b shows a native polyacrylamide gel electrophoresis (PAGE) analysis of the assembled enzyme complex, together with various sub-complexes. Both the gel results and the chromatogram resulting from sizeexclusion chromatography ( Supplementary Fig. S21) demonstrate assembly of the G6pDH-NAD + -MDH swinging arm cascade with >80% yield. The assembled mixture was further purified by size exclusion chromatography for enzyme activity assays. Assembly of the complete complex was also visualized by atomic force microscopy (AFM) ( Fig. 1c and Supplementary Fig. S57 for larger view images), where the presence of the enzymes on the structure is confirmed by differences in height ("brightness") compared to the surface of the DNA tile.To first explore the parameters and understand the kinetics and mechanism of the restricted diffusion mediated by the ssDNA swinging arm, we developed a simplified model system ( Supplementary Fig. S22). In this model, a Cy3 reporter dye takes the place of NAD + on the single-stranded poly(T) 20 arm, whereas a BHQ fluorescence quencher and a Cy5 energy transfer acceptor dye replace one or both enzymes on selected probe positions surrounding the swinging arm (Fig. 2a). An oligonucleotide sequence (5'-ATA GTG AAA) was extended from the 5' end of the poly(T) 20 sequence and positioned halfway between the quencher and acceptor, allowing the arm to transiently hybridize to the probes that each bear the complementary sequence (5'-TTT CAC TAT) in analogy to the binding of NAD + /NADH to the dehydrogenases. To characterize the distance dependence of the diffusive transport and binding mediated by the swinging arm using smFRET, we chose a design in which a single Cy5-labeled capture probe was placed at one of three topologically accessible distances from the Cy3-labeled arm: 7 nm (21 base pairs), 14 nm (42 base pairs) and 21 nm (63 base pairs). As shown in Fig. 2b, the most efficient hybridization to the capture probe was observed at 7 nm, where ~94% of all swinging arms were associated with the Cy5 probe at equilibrium (leading to high FRET). As the distance increased, the equilibrium fraction of captured swinging arms decreased to ~58% at 14 nm and only ...
The functions of regulatory enzymes are essential to modulating cellular pathways. Here, we report a tweezer-like DNA nanodevice to actuate the activity of an enzyme/cofactor pair. A dehydrogenase and NAD þ cofactor are attached to different arms of the DNA tweezer structure and actuation of enzymatic function is achieved by switching the tweezers between open and closed states. The enzyme/cofactor pair is spatially separated in the open state with inhibited enzyme function, whereas in the closed state, enzyme is activated by the close proximity of the two molecules. The conformational state of the DNA tweezer is controlled by the addition of specific oligonucleotides that serve as the thermodynamic driver (fuel) to trigger the change. Using this approach, several cycles of externally controlled enzyme inhibition and activation are successfully demonstrated. This principle of responsive enzyme nanodevices may be used to regulate other types of enzymes and to introduce feedback or feed-forward control loops.
Summary Influenza viruses remain a major public health threat. Seasonal influenza vaccination in humans primarily stimulates pre-existing memory B cells, leading to a transient wave of circulating antibody-secreting plasmablasts 1 – 3 . This recall response contributes to “original antigenic sin,” the selective boosting of antibody specificities from prior exposures to influenza virus antigens 4 . It remains unclear whether such vaccination can also induce germinal centre (GC) reactions in the draining lymph node (LN) where diversification and maturation of recruited B cells can occur 5 . Here we used ultrasound-guided fine needle aspiration to serially sample the draining LNs and investigate the dynamics and specificity of GC B cell responses after influenza vaccination in humans. We show that influenza vaccine-binding GC B cells can be detected as early as 1 week after vaccination. In 3 out of 8 participants, we detected vaccine-binding GC B cells up to 9 weeks after vaccination. Between 12% and 88% of the responding GC B cell clones overlapped with those detected among early circulating plasmablasts. These shared B cell clones had high frequencies of somatic hypermutation (SHM) and encoded broadly cross-reactive monoclonal antibodies (mAbs). In contrast, vaccine-induced B cell clones detected only in the GC compartment exhibited significantly lower SHM frequencies and predominantly encoded strain-specific mAbs, suggesting a naïve B cell origin. Electron microscopy-based epitope mapping revealed that some of these strain-specific mAbs recognized epitopes that were not targeted by the early plasmablast response. Our results indicate that influenza virus vaccination of humans can elicit a GC reaction to which B cell clones targeting novel epitopes are more likely to be recruited, thereby broadening the spectrum of vaccine-induced protective antibodies against this rapidly mutating pathogen.
Engineering wireframe architectures and scaffolds of increasing complexity is one of the important challenges in nanotechnology. We present a design strategy to create gridiron-like DNA structures. A series of four-arm junctions are used as vertices within a network of double-helical DNA fragments. Deliberate distortion of the junctions from their most relaxed conformations ensures that a scaffold strand can traverse through individual vertices in multiple directions. DNA gridirons were assembled, ranging from two-dimensional arrays with reconfigurability to multilayer and three-dimensional structures and curved objects.
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