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The evolution of dynamic DNA nanostructures has propelled DNA nanotechnology into a robust and versatile field, offering groundbreaking applications in nanoscale communication, drug delivery, and molecular computing. Yet, the full potential of this technology awaits further enhancement through optimization of kinetic properties governing conformational changes. In this work, we introduce a mean-field theory to characterize the kinetic behavior of a dynamic DNA origami hinge where each arm bears complementary single-stranded DNA overhangs of different lengths, which can latch the hinge at a closed conformation. This device is currently being investigated for multiple applications, being of particular interest the development of DNA-based rapid diagnostic tests for coronavirus. Drawing from classical statistical mechanics theories, we derive analytical expressions for the mean binding time of these overhangs within a constant hinge. This analysis is then extended to flexible hinges, where the angle diffuses within a predetermined energy landscape. We validate our model by comparing it with experimental measurements of the closing rates of DNA nanocalipers with different energy landscapes and overhang lengths, demonstrating excellent agreement and suggesting fast angular relaxation relative to binding. These findings offer insights that can guide the optimization of devices for specific state lifetimes. Moreover, the framework introduced here lays the groundwork for further advancements in modeling the kinetics of dynamic DNA nanostructures. [ABSTRACT FROM AUTHOR]

The folding of RNA and DNA strands plays crucial roles in biological systems and bionanotechnology. However, studying these processes with high-resolution numerical models is beyond current computational capabilities due to the timescales and system sizes involved. In this article, we present a new coarse-grained model for investigating the folding dynamics of nucleic acids. Our model represents three nucleotides with a patchy particle and is parameterized using well-established nearest-neighbor models. Thanks to the reduction of degrees of freedom and to a bond-swapping mechanism, our model allows for simulations at timescales and length scales that are currently inaccessible to more detailed models. To validate the performance of our model, we conducted extensive simulations of various systems: We examined the thermodynamics of DNA hairpins, capturing their stability and structural transitions, the folding of an MMTV pseudoknot, which is a complex RNA structure involved in viral replication, and also explored the folding of an RNA tile containing a k-type pseudoknot. Finally, we evaluated the performance of the new model in reproducing the melting temperatures of oligomers and the dependence on the toehold length of the displacement rate in toehold-mediated displacement processes, a key reaction used in molecular computing. All in all, the successful reproduction of experimental data and favorable comparisons with existing coarse-grained models validate the effectiveness of the new model. [ABSTRACT FROM AUTHOR]

Reconfigurable chiral plasmonic complexes are fabricated by planar assembly of multiple individual gold nanorod dimers using DNA origami templates. Additionally, each chiral center can be controlled to switch among achiral, left-handed, and right-handed states. We demonstrate that their overall circular dichroism is determined by the coupling of individual chiral centers and is heavily influenced by the precise number and arrangement of these centers. Our study offers a novel self-assembly method for constructing intricate and dynamic chiral plasmonics as well as investigating the interactions among several plasmonic chiral centers. [ABSTRACT FROM AUTHOR]

DNA nanostructures have shown great potential in biomedical fields. However, the immune responses, especially the activation of the cGAS‐STING signaling (A‐cGSs), induced by DNA nanostructures, remain incompletely understood. Here, the ability of various DNA nanostructures from double‐stranded DNA (dsDNA), single‐stranded tiles (SSTs) to DNA origami is investigated on A‐cGSs. Unlike natural dsDNA which triggers potent A‐cGSs, the structural interconnectivity of various DNA configurations can substantially reduce the occurrence of A‐cGSs, irrespective of their form, dimensions, and conformation. However, wireframe DNA nanostructures can activate the cGAS‐STING signaling, suggesting that decreasing A‐cGSs is dsDNA compactness‐dependent. Based on this, a reconfigurable DNA Origami Domino Array (DODA) is used to systematically interrogate how dsDNA influences the A‐cGSs and demonstrates that the length, number, and space of dsDNA array coordinately influence the activation level of cGAS‐STING signaling, realizing a regulation of innate immune response. The above data and findings enhance the understanding of how DNA nanostructures affect cellular innate immune responses and new insights into the modulation of innate immune responses by DNA nanomedicine. [ABSTRACT FROM AUTHOR]

DNA origami nanostructures (DONs) are able to scavenge reactive oxygen species (ROS) and their scavenging efficiency toward ROS radicals was shown to be comparable to that of genomic DNA. Herein, we demonstrate that DONs are highly efficient singlet oxygen quenchers outperforming double‐stranded (ds) DNA by several orders of magnitude. To this end, a ROS mixture rich in singlet oxygen is generated by light irradiation of the photosensitizer methylene blue and its cytotoxic effect on Escherichia coli cells is quantified in the presence and absence of DONs. DONs are found to be vastly superior to dsDNA in protecting the bacteria from ROS‐induced damage and even surpass established ROS scavengers. At a concentration of 15 nM, DONs are about 50 000 times more efficient ROS scavengers than dsDNA at an equivalent concentration. This is attributed to the dominant role of singlet oxygen, which has a long diffusion length and reacts specifically with guanine. The dense packing of the available guanines into the small volume of the DON increases the overall quenching probability compared to a linear dsDNA with the same number of base pairs. DONs thus have great potential to alleviate oxidative stress caused by singlet oxygen in diverse therapeutic settings. [ABSTRACT FROM AUTHOR]

Plasmonic nanoparticles play a pivotal role in various research areas due to their exceptional optical and thermo‐optical properties, like high spectral tunability and efficient light‐to‐heat conversion. Gold, with its biocompatibility, low cytotoxicity, and tunable resonances , makes gold nanoparticles ideal for photothermal therapies. Geometries, including spheres, core–shells, rods, disks, stars, nanocages, and nanotoroids, are extensively studied, with the gold nanodoughnut emerging as one of the most promising ones due to its ability to produce high temperatures and rotational stability. Nevertheless, the fabrication of metallic toroidal shapes remains a challenge. Recent advances in DNA‐based nanotechnology, especially DNA‐origami techniques, provide feasible route for the fabrication of this geometry through metallization reactions or attachment of metal nanoparticles. However, particles manufactured using this method possess a DNA core that influences their thermoplasmonic performance. In this work, a theoretical investigation is conducted on the thermoplasmonic response of DNA‐origami‐based core/shell toroids (CSTs) for photothermal applications. Key parameters that optimize the CST thermoplasmonic response are identified, and compared with their solid counterparts and discrete metallic coatings. Additionally, the CSTs tolerance to random rotations is assessed, providing insights into their behavior in fluidic environments and implications for its practical consideration. [ABSTRACT FROM AUTHOR]

DNA nanostructures, known for their programmability, ease of modification, and favourable biocompatibility, have gained widespread application in the biomedical field. Among them, Tetrahedral DNA Origami (TDOs), as a novel DNA nanostructure, possesses well‐defined structures, multiple modification sites, and large cavities, making it a promising drug carrier. However, current understanding of TDOs' interactions with biological systems, particularly with target cells and organs, remains unexplored, limiting its further applications in biomedicine. In this work, we prepared TDOs with an average particle size of 40 nm and labelled them with Cy5 fluorescent molecules. Following intravenous injection in mice, the uptake of TDOs by different types of liver and kidney cells was observed. Results indicated that TDOs accumulate in renal tubules and are metabolized by Kupffer cells, epithelial cells, and hepatocytes in the liver. Additionally, in a tumour‐bearing mouse model, TDOs passively targeted tumour tissues and exhibited excellent tumour penetration and retention after rapid metabolism in hepatocytes. Our findings provide crucial insights for the development of TDO‐based drug delivery systems. [ABSTRACT FROM AUTHOR]

In this study, we developed DNA origami as a multiple module co-delivery carrier for immunotherapy. Three types of immune stimulators were precisely assembled in the nanocarrier. The doxorubicin (DOX) component induced immunogenic cell death (ICD) of tumor cells and enhanced phagocytosis of antigen-presenting cells (APCs). Exogenous double-stranded DNA (dsDNA) could act as a molecular adjuvant to activate the stimulator of interferon genes (STING) signaling in APCs by engulfing dying tumor cells. The interleukin (IL)-12 plasmid and small hairpin programmed cell death-ligand 1 (shPD-L1) transcription template were designed to regulate TME. By modifying targeting moieties (cRGD) and controlled-release groups (disulfide bonds), multi-modules can be released more effectively at the desired site in a controlled manner. [Display omitted] A major challenge in combining cancer immunotherapy is the efficient delivery of multiple types of immunological stimulators to elicit a robust anti-tumor immune response and reprogram the immunosuppressive tumor microenvironment (TME). Here, we developed a DNA nanodevice that was generated by precisely assembling three types of immunological stimulators. The doxorubicin (Dox) component induced immunogenic cell death (ICD) in tumor cells and enhanced phagocytosis of antigen-presenting cells (APCs). Exogenous double-stranded DNA (dsDNA) could act as a molecular adjuvant to activate the stimulator of interferon genes (STING) signaling in APCs by engulfing dying tumor cells. Interleukin (IL)-12 and small hairpin programmed cell death-ligand 1 (shPD-L1) transcription templates were designed to regulate TME. Additionally, for targeted drug delivery, multiple cyclo[Arg-Gly-Asp-(d -Phe)-Cys] (cRGD) peptide units on DNA origami were employed. The incorporation of disulfide bonds allowed the release of multiple modules in response to intracellular glutathione (GSH) in tumors. The nanodevice promoted the infiltration of CD8+ and CD4+ cells into the tumor and generated a highly inflamed TME, thereby enhancing the effectiveness of cancer immunotherapy. Our research results indicate that the nanodevice we constructed can effectively inhibit tumor growth and prevent lung metastasis without obvious systemic toxicity, providing a promising strategy for cancer combination treatment. [ABSTRACT FROM AUTHOR]

Background: Among mechanoporation techniques for intracellular delivery, microfluidic approaches succeed in high delivery efficiency and throughput. However, especially the entry of large cargoes (e.g. DNA origami, mRNAs, organic/inorganic nanoparticles) is currently impaired since it requires large cell membrane pores with the need to apply multi-step processes and high forces, dramatically reducing cell viability. Results: Here, HiViPore presents as a microfluidic viscoelastic contactless compression for one-step cell mechanoporation to produce large pores while preserving high cell viability. Inducing an increase of curvature at the equatorial region of cells, formation of a pore with a size of ~ 1 μm is obtained. The poration is coupled to an increase of membrane tension, measured as a raised fluorescence lifetime of 12% of a planarizable push-pull fluorescent probe (Flipper-TR) labelling the cell plasma membrane. Importantly, the local disruptions of cell membrane are transient and non-invasive, with a complete recovery of cell integrity and functions in ~ 10 min. As result, HiViPore guarantees cell viability as high as ~ 90%. In such conditions, an endocytic-free diffusion of large nanoparticles is obtained with typical size up to 500 nm and with a delivery efficiency up to 12 times higher than not-treated cells. Conclusions: The proposed one-step contactless mechanoporation results in an efficient and safe approach for advancing intracellular delivery strategies. In detail, HiViPore solves the issues of low cell viability when multiple steps of poration are required to obtain large pores across the cell plasma membrane. Moreover, the compression uses a versatile, low-cost, biocompatible viscoelastic fluid, thus also optimizing the operational costs. With HiViPore, we aim to propose an easy-to-use microfluidic device to a wide range of users, involved in biomedical research, imaging techniques and nanotechnology for intracellular delivery applications in cell engineering. [ABSTRACT FROM AUTHOR]

Plasmonic nanomaterials bearing targeting ligands are of great interest for surface‐enhanced Raman scattering (SERS)‐based bioimaging applications. However, the practical utility of SERS‐based imaging strategies is hindered by the lack of a straightforward method to synthesize highly sensitive SERS‐active nanostructures with high yield and efficiency. In this work, leveraging DNA origami principles, the first‐in‐class design of a SERS‐based plasmonically coupled nanoprobe for targeted cancer imaging (SPECTRA) is reported. The nanoprobe harnesses a cancer cell targeting DNA aptamer sequence and vibrational tag with stretching frequency in the cell‐silent Raman window. Through the integration of aptamer sequence specific for DU145 cells, the unique capabilities of SPECTRA for targeted imaging of DU145 cells are shown. The results demonstrate that the scalability, cost‐effectiveness, and reproducibility of this method of fabrication of SERS nanoprobes can serve as a versatile platform for creating nanoprobes with broad applications in the fields of cancer biology and biomedical imaging. [ABSTRACT FROM AUTHOR]

Current in vitro models struggle to balance the complexity of human diseases with suitability for large-scale drug tests. While 3D cultures simulate human tissues, they lack cellular intricacy, and integrating these models with high-throughput drug screening remains a challenge. Here, we introduce a method that uses self-assembling nucleic acid nanostructures decorated living cells, termed NACs, to create spheroids with a customizable 3D layout. To demonstrate its uniqueness, our method effectively creates designer 3D spheroids by combining parenchymal cells, stromal cells, and immune cells, leading to heightened physiological relevance and detailed modeling of complex chronic diseases and immune-stromal interactions. Our approach achieves a high level of biological fidelity while being standardized and straightforward to construct with the potential for large-scale drug discovery applications. By merging the precision of DNA nanotechnology with advanced cell culture techniques, we are streamlining human-centric models, striking a balance between complexity and standardization, to boost drug screening efficiency. [ABSTRACT FROM AUTHOR]

Stimuli‐responsive patterned photonic actuators, characterized by their patterned nano/microscale structures and capacity to demonstrate synergistic color changes and shape morphing in response to external stimuli, have attracted intense scientific attention. However, traditional patterned photonic actuator systems still face limitations such as cumbersome and time‐consuming preparation processes and small‐scale deformations. Herein, we introduce a facile approach involving an athermal embossing technique to rapidly fabricate patterned photonic actuators based on near‐infrared (NIR) light‐responsive liquid crystal elastomers. The resulting patterned photonic actuators demonstrate remarkable features, including brilliant angle‐dependent structural color, complex three‐dimensional actuation, and good color durability under NIR light stimulation. As illustrative demonstrations of the proof‐of‐concept, we fabricate two light‐fuelled patterned photonic soft actuators: a butterfly‐inspired actuator that can produce wing‐flapping dynamic changes in structural color, and an origami crane‐shaped actuator with shape memory, structural color information storage, and dynamic display properties. This strategy provides distinct insights into the design and fabrication of various patterned photonic soft robotic devices and intelligent actuators. [ABSTRACT FROM AUTHOR]

Cells switch genes ON or OFF by altering the state of chromatin via histone modifications at specific regulatory locations along the chromatin polymer. These gene regulation processes are carried out by a network of reactions in which the histone marks spread to neighboring regions with the help of enzymes. In the literature, this spreading has been studied as a purely kinetic, non-diffusive process considering the interactions between neighboring nucleosomes. In this work, we go beyond this framework and study the spreading of modifications using a reaction-diffusion (RD) model accounting for the diffusion of the constituents. We quantitatively segregate the modification profiles generated from kinetic and RD models. The diffusion and degradation of enzymes set a natural length scale for limiting the domain size of modification spreading, and the resulting enzyme limitation is inherent in our model. We also demonstrate the emergence of confined modification domains without the explicit requirement of a nucleation site. We explore polymer compaction effects on spreading and show that single-cell domains may differ from averaged profiles. We find that the modification profiles from our model are comparable with existing H3K9me3 data of S. pombe. Author summary: DNA is folded into chromatin by wrapping it around histone protein octamers, forming a string of nucleosome beads. The chemical modifications on histone proteins along the one-dimensional string form a significant part of the epigenetic code. This code determines whether a chromatin region is likely to be active or repressed. How the chemical modification patterns arise, and their stability along the histone proteins is a question of great interest. While some players in this process are known, how the physical process of diffusion and reaction of the enzymes collectively dictate the pattern formation is unknown. In this work, we simulate histone modification spreading accounting for explicit diffusion and reaction of the essential constituents. We show that the diffusion and degradation processes of the constituents limit the size of the modification domain. We also show how the availability of enzymes and the compaction of the chromatin affect the spreading of the histone modification. [ABSTRACT FROM AUTHOR]

DNA nanostructures exhibit versatile geometries and possess sophisticated capabilities not found in other nanomaterials. They serve as customizable nanoplatforms for orchestrating the spatial arrangement of molecular components, such as biomolecules, antibodies, or synthetic nanomaterials. This is achieved by incorporating oligonucleotides into the design of the nanostructure. In the realm of drug delivery to cancer cells, there is a growing interest in active targeting assays to enhance efficacy and selectivity. The active targeting approach involves a "key‐lock" mechanism where the carrier, through its ligand, recognizes specific receptors on tumor cells, facilitating the release of drugs. Various DNA nanostructures, including DNA origami, Tetrahedral, nanoflower, cruciform, nanostar, nanocentipede, and nanococklebur, can traverse the lipid layer of the cell membrane, allowing cargo delivery to the nucleus. Aptamers, easily formed in vitro, are recognized for their targeted delivery capabilities due to their high selectivity for specific targets and low immunogenicity. This review provides a comprehensive overview of recent advancements in the formation and modification of aptamer‐modified DNA nanostructures within drug delivery systems. [ABSTRACT FROM AUTHOR]

The adhesion of circulating tumor cells (CTCs) to the endothelial lumen and their extravasation to surrounding tissues are crucial in the seeding of metastases and remain the most complex events of the metastatic cascade to study. Integrins expressed on CTCs are major regulators of the extravasation process. This knowledge is primarily derived from animal models and biomimetic systems based on artificial endothelial layers, but these methods have ethical or technical limitations. We present a versatile microfluidic device to study cancer cell extravasation that mimics the endothelial barrier by using a porous membrane functionalized with DNA origami nanostructures (DONs) that display nanoscale patterns of adhesion peptides to circulating cancer cells. The device simulates physiological flow conditions and allows direct visualization of cell transmigration through microchannel pores using 3D confocal imaging. Using this system, we studied integrin‐specific adhesion in the absence of other adhesive events. Specifically, we show that the transmigration ability of the metastatic cancer cell line MDA‐MB‐231 is influenced by the type, distance, and density of adhesion peptides present on the DONs. Furthermore, studies with mixed ligand systems indicate that integrins binding to RGD (arginine‐glycine‐aspartic acid) and IDS (isoleucine‐aspartic acid‐serine) did not synergistically enhance the extravasation process of MDA‐MB‐231 cells. [ABSTRACT FROM AUTHOR]

DNA origami nanostructures (DOs) are promising tools for applications including drug delivery, biosensing, detecting biomolecules, and probing chromatin substructures. Targeting these nanodevices to mammalian cell nuclei could provide impactful approaches for probing, visualizing, and controlling biomolecular processes within live cells. We present an approach to deliver DOs into live-cell nuclei. We show that these DOs do not undergo detectable structural degradation in cell culture media or cell extracts for 24 hours. To deliver DOs into the nuclei of human U2OS cells, we conjugated 30-nanometer DO nanorods with an antibody raised against a nuclear factor, specifically the largest subunit of RNA polymerase II (Pol II). We find that DOs remain structurally intact in cells for 24 hours, including inside the nucleus. We demonstrate that electroporated anti-Pol II antibody-conjugated DOs are piggybacked into nuclei and exhibit subdiffusive motion inside the nucleus. Our results establish interfacing DOs with a nuclear factor as an effective method to deliver nanodevices into live-cell nuclei. [ABSTRACT FROM AUTHOR]

Topological indices quantify the connectivity and structural properties of chemical compounds. We use the topological indices for predicting and evaluating the numerous properties of molecules, such as boiling temperatures, toxicity, and biological activity. Zagreb connection indices are a useful tool for studying the structural characteristics of the DNA backbone network. These indices provide important information on the arrangement and connections between nucleotide bases inside the DNA molecule. These indices show compactness, complexity, and topological properties in order to predict DNA bending propensity, DNA-protein interaction, and DNA stability. DNA folding patterns and the impact of mutations on DNA networks are areas of further research for these topological indices. In this study, we calculate Zagreb connection indices and modified Zagreb connection indices for backbone DNA network and subdivided backbone DNA network. Furthermore, we compute the hyper-Zagreb connection index, the inverse sum connection index, and the harmonic connection index. [ABSTRACT FROM AUTHOR]

The incorporation of histone variants has structural ramifications on nucleosome dynamics and stability. Due to their unique sequences, histone variants can alter histone–histone or histone–DNA interactions, impacting the folding of DNA around the histone octamer and the overall higher-order structure of chromatin fibers. These structural modifications alter chromatin compaction and accessibility of DNA by transcription factors and other regulatory proteins to influence gene regulatory processes such as DNA damage and repair, as well as transcriptional activation or repression. Histone variants can also generate a unique interactome composed of histone chaperones and chromatin remodeling complexes. Any of these perturbations can contribute to cellular plasticity and the progression of human diseases. Here, we focus on a frequently overlooked group of histone variants lying within the four human histone gene clusters and their contribution to breast cancer. [ABSTRACT FROM AUTHOR]

The finite periodic arrangement of functional nanomaterials on the two‐dimensional scale enables the integration and enhancement of individual properties, making them an important research topic in the field of tuneable nanodevices. Although layer‐controllable lattices such as graphene have been successfully synthesized, achieving similar control over colloidal nanoparticles remains a challenge. DNA origami technology has achieved remarkable breakthroughs in programmed nanoparticle assembly. Based on this technology, we proposed a hierarchical assembly strategy to construct a universal DNA origami platform with customized layer properties, which we called 2.5‐dimensional (2.5D) DNA origami crystals. Methodologically, this strategy divides the assembly procedure into two steps: 1) array synthesis, and 2) lattice synthesis, which means that the layer properties, including layer number, interlayer distance, and surface morphology, can be flexibly customized based on the independent designs in each step. In practice, these synthesized 2.5D crystals not only pioneer the expansion of the DNA origami crystal library to a wider range of dimensions, but also highlight the technological potential for templating 2.5D colloidal nanomaterial lattices. [ABSTRACT FROM AUTHOR]

The label-free, non-destructive information provided by Raman spectroscopy regarding chemical composition, molecular structure, and molecular interaction makes it a potent analytical tool. Raman scattering's low intensity, however, prevents it from being widely used in a variety of sectors. Plasmonic nanoparticles (NPs) on the surface may considerably improve the Raman process, resulting in surface-enhanced Raman scattering (SERS). Due to the capacity to co-assembling many particles in complicated shapes with fine control of stoichiometry, orientation, and gaps between the particles, the creation of plasmonic nanostructures utilizing a bottom-up method using DNA origami has generated considerable scientific interest. We evaluate current developments in the use of DNA origami structures for the creation of SERS-based sensors in this review paper. We go through SERS fundamentals, plasmonic enhancement processes, and several plasmonic nanostructure fabrication techniques. Additionally, we discuss the benefits of DNA origami in the construction of plasmonic NPs and the creation of SERS hotspots for analytical and medicinal uses. We also discuss potential paths for future research and difficulties facing DNA origami-based SERS sensors. This study attempts to provide a thorough grasp of DNA origami's potential in the creation of SERS-based sensors and its possibilities for the future. [ABSTRACT FROM AUTHOR]

DNA origami nanodevices achieve programmable structure and tunable mechanical and dynamic properties by leveraging the sequence‐specific interactions of nucleic acids. Previous advances have also established DNA origami as a useful building block to make well‐defined micron‐scale structures through hierarchical self‐assembly, but these efforts have largely leveraged the structural features of DNA origami. The tunable dynamic and mechanical properties also provide an opportunity to make assemblies with adaptive structures and properties. Here the integration of DNA origami hinge nanodevices and coiled‐coil peptides are reported into hybrid reconfigurable assemblies. With the same dynamic device and peptide interaction, it is made multiple higher‐order assemblies (i.e., polymorphic assembly) by organizing clusters of peptides into patches or arranging single peptides into patterns on the surfaces of DNA origami to control the relative orientation of devices. The coiled‐coil interactions are used to construct circular and linear assemblies whose structure and mechanical properties can be modulated with DNA‐based reconfiguration. Reconfiguration of linear assemblies leads to micron scale motions and ≈2.5‐10‐fold increase in bending stiffness. The results provide a foundation for stimulus‐responsive hybrid assemblies that can adapt their structure and properties in response to nucleic acid, peptide, protein, or other triggers. [ABSTRACT FROM AUTHOR]

The coupling of structural transitions to heat capacity changes leads to destabilization of macromolecules at both elevated and lowered temperatures. DNA origami not only exhibit this property but also provide a nanoscopic observable of cold denaturation processes by directing intramolecular strain to the most sensitive elements within their hierarchical architecture. [ABSTRACT FROM AUTHOR]

The document is a contents list for the journal Chemical Communications, published by The Royal Society of Chemistry. It includes a feature article on the use of tetrazoles in constructing assemblies, as well as several communications on various topics such as electron-poor Au(III) trication, cold denaturation of DNA origami nanostructures, and optical discrimination of terpenes in citrus peels. The journal aims to connect the global chemistry community and publishes work from scientists at all career stages and countries. [Extracted from the article]

Molecular computing is an emerging paradigm that plays an essential role in data storage, bio-computation, and clinical diagnosis with the future trends of more efficient computing scheme, higher modularity with scaled-up circuity and stronger tolerance of corrupted inputs in a complex environment. Towards these goals, we construct a spatially localized, DNA integrated circuits-based classifier (DNA IC-CLA) that can perform neuromorphic architecture-based computation at a molecular level for medical diagnosis. The DNA-based classifier employs a two-dimensional DNA origami as the framework and localized processing modules as the in-frame computing core to execute arithmetic operations (e.g. multiplication, addition, subtraction) for efficient linear classification of complex patterns of miRNA inputs. We demonstrate that the DNA IC-CLA enables accurate cancer diagnosis in a faster (about 3 h) and more effective manner in synthetic and clinical samples compared to those of the traditional freely diffusible DNA circuits. We believe that this all-in-one DNA-based classifier can exhibit more applications in biocomputing in cells and medical diagnostics. Molecular computing is an emerging paradigm with a crucial role in clinical diagnosis. Here, authors develop a spatially localized, DNA-integrated circuits-based classifier, DNA IC-CLA, which enables accurate cancer diagnosis for clinical samples in a faster and more effective manner. [ABSTRACT FROM AUTHOR]

Transmembrane proteins transmit chemical signals as well as mechanical cues. The latter is often achieved by coupling to the cytoskeleton. The incorporation of fully engineerable membrane‐spanning structures for the transduction of chemical and, in particular, mechanical signals is therefore a critical aim for bottom‐up synthetic biology. Here, a membrane‐spanning DNA origami signaling units (DOSUs) is designed and mechanically coupled to DNA cytoskeletons encapsulated within giant unilamellar vesicles (GUVs). The incorporation of the DOSUs into the GUV membranes is verified and clustering upon external stimulation is achieved. Dye‐influx assays reveal that clustering increases the insertion efficiency. The transmembrane‐spanning DOSUs act as pores to allow for the transport of single‐stranded DNA into the GUVs. This is employed to trigger the reconfiguration of DNA cytoskeletons within GUVs. In addition to chemical signaling, mechanical coupling of the DOSUs to the internal DNA cytoskeletons is induced. With chemical cues from the environment, clustering of the DOSUs is induced, which triggers a symmetry break in the organization of the DNA cytoskeleton inside of the GUV. DNA‐based transmembrane structures are engineered that transduce signals without transporting the signaling molecule itself—providing a route toward signal processing and adaptive synthetic cells. [ABSTRACT FROM AUTHOR]

Sophisticated statistical mechanics approaches and human intuition have demonstrated the possibility of self-assembling complex lattices or finite-size constructs. However, attempts so far have mostly only been successful in silico and often fail in experiment because of unpredicted traps associated with kinetic slowing down (gelation, glass transition) and competing ordered structures. Theoretical predictions also face the difficulty of encoding the desired interparticle interaction potential with the experimentally available nano- and micrometer-sized particles. To overcome these issues, we combine SAT assembly (a patchy-particle interaction design algorithm based on constrained optimization) with coarse-grained simulations of DNA nanotechnology to experimentally realize trap-free self-assembly pathways. We use this approach to assemble a pyrochlore three-dimensional lattice, coveted for its promise in the construction of optical metamaterials, and characterize it with small-angle x-ray scattering and scanning electron microscopy visualization. [ABSTRACT FROM AUTHOR]

Colloidal self-assembly allows rational design of structures on the micrometer and submicrometer scale. One architecture that can generate complete three-dimensional photonic bandgaps is the diamond cubic lattice, which has remained difficult to realize at length scales comparable with the wavelength of visible or ultraviolet light. In this work, we demonstrate three-dimensional photonic crystals self-assembled from DNA origami that act as precisely programmable patchy colloids. Our DNA-based nanoscale tetrapods crystallize into a rod-connected diamond cubic lattice with a periodicity of 170 nanometers. This structure serves as a scaffold for atomic-layer deposition of high-refractive index materials such as titanium dioxide, yielding a tunable photonic bandgap in the near-ultraviolet. [ABSTRACT FROM AUTHOR]

Introduction: DNA barcoding in insects has progressed rapidly, with the ultimate goal of a complete inventory of the world's species. However, the barcoding effort to date has been driven by a few national campaigns and leaves much of the world unsampled. This study investigates to what degree the current barcode data cover the species diversity across the globe, using the leaf beetle family Chrysomelidae as an example. Methods: A recent version (June 2023) of the Barcode-of-Life database was subjected to test of sampling completeness using the barcode-to-BIN ratio and sampling coverage (SC) metric. All barcodes were placed in a phylogenetic tree of ~600 mitochondrial genomes, applying phylogenetic diversity (PD) and metrics of community phylogenetics to national barcode sets to test for sampling completeness at clade level and reveal the global structure of species diversity. Results: The database included 73342 barcodes, grouped into 5310 BINs (species proxies) from 101 countries. Costa Rica contributed nearly half of all barcode sequences, while nearly 50 countries were represented by less than ten barcodes. Only five countries, Costa Rica, Canada, South Africa, Germany, and Spain, had a high sampling completeness, although collectively the barcode database covers most major taxonomic and biogeographically confined lineages. PD showed moderate saturation as more species diversity is added in a country, and community phylogenetics indicated clustering of national faunas. However, at the species level the inventory remained incomplete even in the most intensely sampled countries, and the sampling was insufficient for assessment of global species richness patterns. Discussion: The sequence-based inventory in Chrysomelidae needs to be greatly expanded to include more areas and deeper local sampling before reaching a knowledge base similar to the existing Linnaean taxonomy. However, placing the barcodes into a backbone phylogenetic tree from mitochondrial genomes, a taxonomically and biogeographically highly structured pattern of global diversity emerges into which all species can be integrated via their barcodes. [ABSTRACT FROM AUTHOR]

Background: Myeloid-derived suppressor cells (MDSCs) promote tumor growth, metastasis, and lead to immunotherapy resistance. Studies revealed that miRNAs are also expressed in MDSCs and promote the immunosuppressive function of MDSCs. Currently, few studies have been reported on inducible cellular microvesicle delivery of nucleic acid drugs targeting miRNA in MDSCs for the treatment of malignant tumors. Results and conclusion: In this study, we designed an artificial DNA named G-quadruplex-enhanced circular single-stranded DNA-9 (G4-CSSD9), that specifically adsorbs the miR-9 sequence. Its advanced DNA folding structure, rich in tandem repeat guanine (G-quadruplex), also provides good stability. Mesenchymal stem cells (MSCs) were prepared into nanostructured vesicles by membrane extrusion. The MSC microvesicles-encapsulated G4-CSSD9 (MVs@G4-CSSD9) was delivered into MDSCs, which affected the downstream transcription and translation process, and reduced the immunosuppressive function of MDSCs, so as to achieve the purpose of treating melanoma. In particular, it provides an idea for the malignant tumor treatment. [ABSTRACT FROM AUTHOR]

In recent years, the field of structural DNA nanotechnology has advanced rapidly due to transformative design tools. Although these tools have been revolutionary, they still bear one overall limitation of requiring users to fully conceptualize their designs before designing. Recently, a simple computational casting technique was developed using generative optimization strategies to automate the DNA origami nanostructure design. This approach employs a shape annealing algorithm, which creates a formal language of honeycomb nanostructures with shape grammars and drives designs from the language toward a desired configuration using simulated annealing. This initial demonstration of the approach can generate novel scaffold routing schemes for creating solid or hollow structures constrained by the boundaries of polyhedral meshes. The results from the initial approach, particularly from the hollow structures, reveal a challenging design space. This simple technique generates novel scaffold routing schemes that do not replicate the overall polyhedral mesh shape and are limited in their ability to control scaffold path exploration in the design space. This paper demonstrates an approach for achieving different levels of consistent effective wall thicknesses and improving the quality of mesh coverage for hollow structures that can be tuned and optimized by introducing a more refined computational casting technique. We achieve these improvements through changes in the simulated annealing algorithm by adding a Hustin move set algorithm that dynamically adjusts the performance of the overall design and redefining how these hollow designs are articulated. This work illustrates how the technique can navigate a challenging design space to generate effective hollow designs. [ABSTRACT FROM AUTHOR]

We propose and investigate an extension of the Caspar--Klug symmetry principles for viral capsid assembly to the programmable assembly of size-controlled triply periodic polyhedra, discrete variants of the Primitive, Diamond, and Gyroid cubic minimal surfaces. Inspired by a recent class of programmable DNA origami colloids, we demonstrate that the economy of design in these crystalline assemblies--in terms of the growth of the number of distinct particle species required with the increased size-scale (e.g., periodicity)--is comparable to viral shells. We further test the role of geometric specificity in these assemblies via dynamical assembly simulations, which show that conditions for simultaneously efficient and high-fidelity assembly require an intermediate degree of flexibility of local angles and lengths in programmed assembly. Off-target misassembly occurs via incorporation of a variant of disclination defects, generalized to the case of hyperbolic crystals. The possibility of these topological defects is a direct consequence of the very same symmetry principles that underlie the economical design, exposing a basic tradeoff between design economy and fidelity of programmable, size controlled assembly. [ABSTRACT FROM AUTHOR]

Metal-mediated base pairing of DNA has been a topic of extensive research spanning over more than four decades. Precise positioning of a single metal ion by predetermining the DNA sequence, as well as improved conductivity offered by the ions, make these structures interesting candidates in the context of using DNA in nanotechnology. Here, we report the formation and characterization of conjugates of long (kilo bases) homoguanine DNA strands with silver ions. We demonstrate using atomic force microscopy (AFM) and scanning tunneling microscope (STM) that binding of silver ions leads to folding of homoguanine DNA strands in a "hairpin" fashion to yield double-helical, left-handed molecules composed of G-G base pairs each stabilized by a silver ion. Further folding of the DNA–silver conjugate yields linear molecules in which the two halves of the double helix are twisted one against the other in a right-handed fashion. Quantum mechanical calculations on smaller molecular models support the helical twist directions obtained by the high resolution STM analysis. These long guanine-based nanostructures bearing a chain of silver ions have not been synthesized and studied before and are likely to possess conductive properties that will make them attractive candidates for nanoelectronics. [ABSTRACT FROM AUTHOR]

Single‐stranded DNA oligonucleotides wrapping on the surface of single‐walled carbon nanotubes (SWCNTs), described as DNA corona, are often used as a dispersing agent for SWCNTs. The uneven distribution of DNA corona along SWCNTs is related to the photoelectric properties and the surface activity of SWCNTs. An ionic strength‐mediated "DNA corona defects" (DCDs) strategy is proposed to acquire an exposed surface of SWCNTs (accessible surface) as large as possible while maintaining good dispersibility via modulating the conformation of DNA corona. By adjusting the solution ionic strength, the DNA corona phase transitioned from an even‐distributed and loose conformation to a locally compact conformation. The resulting enlarged exposed surface of SWCNTs is called DCDs, which provide active sites for molecular adsorption. This strategy is applied for the arrangement of SWCNTs on DNA origami. SWCNTs with ≈11 nm DCD, providing enough space for the adsorption of "capture ssDNA" (≈7 nm width required for 24‐nt) extended from DNA origami structures are fabricated. The DCD strategy has potential applications in SWCNT‐based optoelectronic devices. [ABSTRACT FROM AUTHOR]

Emerging nano-kirigami/origami technology enables the flexible transformations of 2D planar patterns into exquisite 3D structures in situ and has aroused great interest in the areas of nanophotonics and optoelectronics. This paper briefly reviews some milestone research and breakthrough progresses in nano-kirigami/origami from the aspects of stimuli approaches and application directions. Versatile stimuli for kirigami/origami, including capillary force, residual stress, mechanical force, and irradiation-induced stress, are introduced in the micro/nanoscale region. Appealing optical applications and reconfigurable schemes of nano-kirigami/origami structures are summarized, offering effective routes to realize tunable nanophotonic and optoelectronic devices. Future challenges and promising pathways are also envisioned, including design methods, innovative materials, multi-physics field driving, and reprogrammable devices. [ABSTRACT FROM AUTHOR]

Deoxyribonucleic acid (DNA) origami enables the synthesis of bespoke nanoscale structures suitable for diverse applications. Effective design requires preventing uncontrolled aggregation, while still facilitating directed multi‐subunit assembly. Uncontrolled aggregation is often caused by base‐stacking interactions between arrays of blunt‐ended helices, a problem which is typically mitigated by incorporating disordered single‐stranded DNA (ssDNA) (like scaffold loops or poly‐thymine brushes) at the end of double‐stranded DNA (dsDNA) helices. Such disordered regions are ubiquitous in DNA origami structures yet their optimal design requirements in various chemical environments remains unclear. This study systematically investigates scaffold loops and poly‐nucleotide brushes for aggregation prevention and control of multi‐subunit assembly, examining length, sequence, and MgCl2 concentration dependencies. Additionally, a novel strategy is introduced using orthogonal double‐stranded DNA helices to create a steric shield against base stacking. The results reveal key considerations. Poly‐thymine brushes excel in achieving monodispersity across diverse conditions whereas scaffold loops aid directed multi‐subunit assembly. Orthogonal DNA helices remove the need for disordered regions altogether, preventing aggregation over a broad range of MgCl2 concentrations and facilitating controlled multi‐subunit assembly. This study expands the toolbox for DNA origami design and enables a more informed approach for achieving control of monodispersity and multi‐subunit assembly in DNA origami structures. [ABSTRACT FROM AUTHOR]

We present here a 3D-printed pressure mapping mat, equipped with customizable architecture sensors, that offers a cost-effective and adaptable solution, overcoming the size constraints and sensing accuracy issues commonly associated with existing commercial pressure mats across various fields, such as healthcare and sports applications. Leveraging a pillar-origami structure, the demonstrated sensor offers multifaceted stiffness properties, effectively filtering skin deformations and enabling capacitive pressure sensing. Notably, the sensor's detection range can be finely tuned, spanning from 70 to 2500 kPa, with a sensitivity range between 0.01 kPa-1 and 0.0002 kPa-1, and an impressive response time of just 800 milliseconds. Furthermore, the inclusion of a modular sensor array enhances maintenance and allows for greater flexibility in shaping and enhancing the device's resolution. This technology finds practical applications in wireless foot pressure mapping and sports protection pads, marking a significant milestone in the advancement of flexible and custom-shaped pressure sensor technology. [ABSTRACT FROM AUTHOR]

Copyright of Nachrichten aus der Chemie is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Nachrichten aus der Chemie is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Xeno‐nucleic acids (XNAs) are synthetic genetic polymers with improved biological stabilities and offer powerful molecular tools such as aptamers and catalysts. However, XNA application has been hindered by a very limited repertoire of tool enzymes, particularly those that enable de novo XNA synthesis. Here we report that terminal deoxynucleotide transferase (TdT) catalyzes untemplated threose nucleic acid (TNA) synthesis at the 3' terminus of DNA oligonucleotide, resulting in DNA‐TNA chimera resistant to exonuclease digestion. Moreover, TdT‐catalyzed TNA extension supports one‐pot batch preparation of biostable chimeric oligonucleotides, which can be used directly as staple strands during self‐assembly of DNA origami nanostructures (DONs). Such TNA‐protected DONs show enhanced biological stability in the presence of exonuclease I, DNase I and fetal bovine serum. This work not only expands the available enzyme toolbox for XNA synthesis and manipulation, but also provides a promising approach to fabricate DONs with improved stability under the physiological condition. [ABSTRACT FROM AUTHOR]

In order to rapidly and accurately evaluate the mechanical properties of a novel origami-inspired tube structure with multiple parameter inputs, this study developed a method of designing origami-inspired braces based on machine learning models. Four geometric parameters, i.e., cross-sectional side length, plate thickness, crease weakening coefficient, and plane angles, were used to establish a mapping relationship with five mechanical parameters, including elastic stiffness, yield load, yield displacement, ultimate load, and ultimate displacement, all of which were calculated from load-displacement curves. Firstly, forward prediction models were trained and compared for single and multiple mechanical outputs. The parameter ranges were extended and refined to improve the predicted results by introducing the intrinsic mechanical relationships. Secondly, certain reverse prediction models were established to obtain the optimized design parameters. Finally, the design method of this study was verified in finite element methods. The design and analysis framework proposed in this study can be used to promote the application of other novel multi-parameter structures. [ABSTRACT FROM AUTHOR]

Thermoelectric devices (TEDs) show great potential for waste heat energy recycling and sensing. However, existing TEDs cannot be self‐adapted to the complex quadratic surface, leading to significant heat loss and restricting their working scenario. Here, surface‐conformable origami‐TEDs (o‐TEGs) are developed through programmable crease‐designed origami substrates and the screen‐printing TE legs. Compared with "π" structured TEDs, the origami design (with heat conductive materials) changed the heat‐transferring direction of the laminated TE legs, resulting in an enhancement in enlarging ΔT/THot and Vout by 5.02 and 3.51 times. Four o‐TEDs with different creases designs are fabricated to verify the heat recycling ability on plane and central quadratic surfaces. Demonstrating a high Vout density (up to 0.98 −2at ΔT of 50 K) and good surface conformability, o‐TEDs are further used in thermal touch panels attached to multiple surfaces, allowing information to be wirelessly transferred on a remote display via finger‐writing. [ABSTRACT FROM AUTHOR]

Sepsis, defined as a life-threatening organ dysfunction, is associated with increased mortality in individuals with diabetes mellitus. In sepsis under diabetic conditions (SUDC), the superimposed inflammatory response and excessive production of reactive oxygen species (ROS) can cause severe damage to the kidney and liver, making it challenging to effectively repair multi-organ injury. In this study, we report the development of a DNA-based bifunctional nanomedicine, termed IL10-rDON, generated by assembling interleukin 10 (IL10) with rectangular DNA origami nanostructures (rDON) to address multi-organ dysfunction in SUDC. IL10-rDON was shown to predominantly accumulate in the kidney and liver of diabetic mice in vivo and effectively alleviate inflammatory responses through its anti-inflammatory IL10 component. In addition, the consumption of rDON itself significantly reduced excessive ROS in the liver and kidney. Serum and histological examinations further confirmed that IL10-rDON treatment could effectively improve liver and kidney function, as well as the survival of mice with SUDC. This study demonstrates an attractive antioxidant and anti-inflammatory nanomedicine for addressing acute liver and renal failure. The integration of rDON with therapeutic agents using DNA nanotechnology is a promising strategy for generating multifunctional nanomedicine to treat multi-organ dysfunction and other complicated diseases. Sepsis under diabetic conditions (SUDC) leads to high mortality due to multiple organ failure such as acute liver and kidney injury. The anti-inflammatory cytokine interleukin 10 (IL10) holds great potential to treat SUDC, while disadvantages of IL-10 such as short half-life, non-specific distribution and lack of antioxidant activities limit its wide clinical applications. In this study, we developed a DNA-based, bifunctional nanomedicine (IL10-rDON) by assembling IL10 with rectangular DNA origami nanostructures (rDON). We found that IL10-rDON preferentially accumulated and sufficiently attenuated the increased levels of ROS and inflammation in the kidney and liver injury sites, and eventually improved the survival rate of mice with SUDC. Our finding provides new insights into the application of DNA-based nanomedicine in treating multi-organ failure. [Display omitted] [ABSTRACT FROM AUTHOR]

Janus base nanotubes are novel, self-assembled nanomaterials. Their original designs were inspired by DNA base pairs, and today a variety of chemistries has developed, distinguishing them as a new family of materials separate from DNA origami, carbon nanotubes, polymers, and lipids. This review article covers the principal examples of self-assembled Janus base nanotubes, which are driven by hydrogen-bond and n-n stacking interactions in aqueous environments. Specifically, self-complementary hydrogen bonds organize molecules into ordered arrays, forming macrocycles, while n-n interactions stack these structures to create tubular forms. This review elucidates the molecular interactions that govern the assembly of nanotubes and advances our understanding of nanoscale self-assembly in water. [ABSTRACT FROM AUTHOR]

DNA quadruplex structures provide an additional layer of regulatory control in genome maintenance and gene expression and are widely used in nanotechnology. We report the discovery of an unprecedented tetrastranded structure formed from a native G‐rich DNA sequence originating from the telomeric region of Caenorhabditis elegans. The structure is defined by multiple properties that distinguish it from all other known DNA quadruplexes. Most notably, the formation of a stable so‐called KNa‐quadruplex (KNaQ) requires concurrent coordination of K+ and Na+ ions at two distinct binding sites. This structure provides novel insight into G‐rich DNA folding under ionic conditions relevant to eukaryotic cell physiology and the structural evolution of telomeric DNA. It highlights the differences between the structural organization of human and nematode telomeric DNA, which should be considered when using C. elegans as a model in telomere biology, particularly in drug screening applications. Additionally, the absence/presence of KNaQ motifs in the host/parasite introduces an intriguing possibility of exploiting the KNaQ fold as a plausible antiparasitic drug target. The structure's unique shape and ion dependency and the possibility of controlling its folding by using low‐molecular‐weight ligands can be used for the design or discovery of novel recognition DNA elements and sensors. [ABSTRACT FROM AUTHOR]

This paper presents original research developed during PhD research. It proposes a multidisciplinary process as a methodology for the construction of thick, rigid origami surfaces to be used for kinetic architectural purposes. Origami surfaces that fold rigidly allow for strict geometry-based simulations that can reproduce rigorous rigid kinematics from the unfolded to the completely folded state, which is particularly important in large scale structures where motion must be predictable. The considered surfaces are regularly tessellated and have planar initial and final states. Through movement, these can assume a cycle of folding states with different three-dimensional configurations. The proposed method departs from concept, moves to geometry definition, kinematic simulation, structural evaluation, construction, and implementation for folding surfaces. It includes steps for evaluation and correction of issues as well as strategies for construction through digital fabrication with planar, thick materials. Its validity is demonstrated by its application in a constructed case study. [ABSTRACT FROM AUTHOR]

The study of (n × m , k , λ a , λ c) -geometric orthogonal codes ( (n × m , k , λ a , λ c) -GOCs) is motivated by the application in DNA origami. The central research on GOCs is to determine the value of Φ (n × m , k , λ a , λ c) , i.e., the largest possible size among all (n × m , k , λ a , λ c) -GOCs. When λ a = λ c , the exact values of Φ (n × m , 3 , 1 , 1) and Φ (n × m , k , k - 1 , k - 1) were recently determined by Wang and Su et al. In this paper, we research on the cases of λ c = k - 1 and λ a ≤ k - 2 . We determine the exact values of Φ (n × m , k , k - 2 , k - 1) and Φ (n × m , k , k - 3 , k - 1) , and give a calculation method of Φ (n × m , k , λ a , k - 1) with λ a ≤ k - 4 for any positive integers n, m and k. [ABSTRACT FROM AUTHOR]

The natural micro‐ and nanoscale organization of biomacromolecules is a remarkable principle within living cells, allowing for the control of cellular functions by compartmentalization, dimensional diffusion and substrate channeling. In order to explore these biological mechanisms and harness their potential for applications such as sensing and catalysis, molecular scaffolding has emerged as a promising approach. In the case of synthetic enzyme cascades, developments in DNA nanotechnology have produced particularly powerful scaffolds whose addressability can be programmed with nanometer precision. In this minireview, we summarize recent developments in the field of biomimetic multicatalytic cascade reactions organized on DNA nanostructures. We emphasize the impact of the underlying design principles like DNA origami, efficient strategies for enzyme immobilization, as well as the importance of experimental design parameters and theoretical modeling. We show how DNA nanostructures have enabled a better understanding of diffusion and compartmentalization effects at the nanometer length scale, and discuss the challenges and future potential for commercial applications. [ABSTRACT FROM AUTHOR]

Encoded nanostructures afford an ideal platform carrying multi‐channel signal components for multiplexed assay and information security. However, with the demand on exclusivity and reproducibility of coding signals, precise control on the structure and composition of nanomaterials featuring fully distinguishable signals remains challenging. By using the multiplexing capability of mass spectrometry (MS) and spatial addressability of DNA origami nanostructures, we herein propose a quality control methodology for constructing mass‐encoded nanodevices (namely MNTs‐TDOFs) in the scaffold of compartmented tetrahedral DNA origami frames (TDOFs), in which the arrangement and stoichiometry of four types of mass nanotags (MNTs) can be finely regulated and customized to generate characteristic MS patterns. The programmability of combinatorial MNTs and orthogonality of individual compartments allows further evolution of MNTs‐TDOFs to static tagging agents and dynamic nanoprobes for labeling and sensing of multiple targets. More importantly, structure control at single TDOF level ensures the constancy of prescribed MS outputs, by which a high‐capacity coding system was established for secure information encryption and decryption. In addition to the multiplexed outputs in parallel, the nanodevices could also map logic circuits with interconnected complexity and logic events of c‐Met recognition and dimerization on cell surface for signaling regulation by MS interrogation. [ABSTRACT FROM AUTHOR]

There have been limited efforts to ligate the staple nicks in DNA origami which is crucial for their stability against thermal and mechanical treatments, and chemical and biological environments. Here, two near quantitative ligation methods are demonstrated for the native backbone linkage at the nicks in origami: i) a cosolvent dimethyl sulfoxide (DMSO)‐assisted enzymatic ligation and ii) enzyme‐free chemical ligation by CNBr. Both methods achieved over 90% ligation in 2D origami, only CNBr‐method resulted in ≈80% ligation in 3D origami, while the enzyme‐alone yielded 31–55% (2D) or 22–36% (3D) ligation. Only CNBr‐method worked efficiently for 3D origami. The CNBr‐mediated reaction is completed within 5 min, while DMSO‐method took overnight. Ligation by these methods improved the structural stability up to 30 °C, stability during the electrophoresis and subsequent extraction, and against nuclease and cell lysate. These methods are straightforward, non‐tedious, and superior in terms of cost, reaction time, and efficiency. [ABSTRACT FROM AUTHOR]