Nanoscale Space Research Articles

Cargo Quantification of Functionalized DNA Origami for Therapeutic Application.

In recent years, notable advances in nanotechnology-based drug delivery have emerged. A particularly promising platform in this field is DNA origami-based nanoparticles, which offer highly programmable surfaces, providing precise control over the nanoscale spacing and stoichiometry of various cargo. These versatile particles are finding diverse applications ranging from basic molecular biology to diagnostics and therapeutics. This growing interest creates the need for effective methods to quantify cargo on DNA origami nanoparticles. The study consolidates several previously validated methods focusing on gel-based and fluorescence-based techniques, including multiplexed quantification of protein, peptide, and nucleic acid cargo on these nanoparticles. In this work, how gel band intensity and nanodrop fluorescence readings can be used to quantify protein, peptide, and RNA cargo on a DNA origami nanoparticle is demonstrated. This work may serve as a valuable resource for groups of researchers keen on utilizing DNA origami-based nanoparticles in therapeutic applications.

A Complex Concentrated Alloy with Record-High Strength-Toughness at 77 K.

High strength and large ductility, leading to a high material toughness (area under the stress-strain curve), are desirable for alloys used in cryogenic applications. Assisted by domain-knowledge-informed machine learning, here a complex concentrated Fe35Co29Ni24Al10Ta2 alloy is designed, which uses L12 coherent nanoprecipitates in a high volume fraction (≈65 ± 3 vol.%) in a face-centered-cubic (FCC) solid solution matrix that undergoes FCC-to-body-centered-cubic (BCC) phase transformation upon tensile straining. Unlike FCC-to-BCT phase transformation involving brittle carbon-enriched martensite, the BCC martensite in this alloy does not cause brittleness at 77 K. The Fe35Co29Ni24Al10Ta2 multi-principal element alloy achieves a high yield strength ≈1.4GPa, a high work hardening rate >4GPa, an ultimate tensile strength ≈2.25GPa, and a large uniform elongation ≈45%, leading to record-high material toughness compared with previous cryogenic alloys such as 316L series stainless steels and recent high-entropy alloys. The nanoprecipitates with nanoscale spacing (≈7.5nm), apart from serving as dislocation obstacles for strengthening and dislocation sources for sustainable ductility, also undergo deformation twinning. Taken together, these mechanisms are found to be highly effective in strengthening and strain hardening upon tensile straining at liquid nitrogen temperature. These findings demonstrate how to effectively integrate strengthening mechanisms to synergize superior mechanical properties in special-purpose alloys.

The influence of tectonic action on the characteristics of microcrystalline and pore structure of anthracite in Qianbei Coalfield

Tectonic action strongly impacts the coal's microcrystalline and pore structural features. X-ray diffraction (XRD) was employed to analyze the impact of tectonic action on the microcrystalline structure of coal. The pore structure of anthracite was investigated through electron microscope image, mercury intrusion porosimetry and low pressure N2/CO2 adsorption, with a focus on exploring the relationship between the microcrystalline structure of coal and its micropore structure. The results show that under tectonic action, interlayer spacing of the aromatic layer d002 decreases from 0.345 to 0.342 nm, the stacking height Lc decreases from 2.73 to 2.23 nm, the average number of the effective aromatic layer Nave slightly decreases from 6.61 to 6.51, and the crystallite diameter La increases by 0.13 nm, which indicates that tectonic action changes the microcrystalline structure of anthracite. The microcrystalline structure changes from "short and thick" to "long and thin", thus schematic diagram of the anthracite basic structural unit (BSU) under tectonic action was established. The fa of tectonic coal increased by 16.92% compared with that of original coal, and the g increased from 0.85 (original) to 0.89 (tectonic), indicating that the process of aromatization and graphitization of coal was accelerated by tectonic action. Tectonic action plays an important role in promoting pore development, which makes the pore surface of anthracite more rough, the lattice fringe more dense and clear, and increases the pore volume and specific surface area of anthracite by 1.21 and 1.08 times, respectively. Tectonic action can change the BSU of coal, thus producing more nanoscale space. This study holds important implications for comprehending how tectonic action affect the microcrystalline structure of coal as well as its relationship with nanopore structures in tectonic coal.

Operando Studies Redirect Spatiotemporal Restructuration of Model Coordinated Oxides in Electrochemical Oxidation.

Tetrahedral, pyramidal, and octahedral metal-oxygen coordinated ligands are fundamental components in all metal-oxide structures. Understanding the impacts of their spatiotemporal behaviors during electrochemical oxidation is crucial for diverse applications, yet remains unsolved due to challenges in designing model oxides and conducting operando characterizations. Herein, combining a suite of advanced operando characterizations and systematic computations, a link between oxygen-evolving performance and operational structural properties is established on model oxides. Compared with tetrahedral and octahedral structures, pyramidal structure is more susceptible to OH- attack due to its pristine unsaturated and asymmetric features and constant single-electron occupancy on the active z2 orbital during reaction, leading to surface-to-bulk restructuration into active amorphous high-valence CoOOHx with edge-sharing configurations. This is accompanied by ion leaching to create nanoscale space, following a leaching tendency of Sr2+ > Ba2+ > La3+ > Y3+. Operando soft X-ray absorption spectroscopy demonstrates a harder non-uniform dehydrogenation process over time (Co3+OOH → Co3+/4+OOHx → Co4+OO) because of the enhanced CoO covalency with higher energy barriers. Lattice oxygen participates in active CoOOHx formation but sacrifices stability. To address this activity-stability trade-off, an ion-tuning strategy is proposed to simultaneously enhance both activity and stability in electrode and device.

A refined model of lithium-ion battery considering agglomerated active material and non-uniform graphite particle

This study presents a refined lithium-ion battery model based on the Newman model, incorporating agglomerate structures in the positive electrode and non-uniform particle size distribution in the negative electrode. The agglomerates in the positive region consist of nano-scale primary particles, pore spaces, and binders, while the negative region features a random distribution of particle sizes. The model employs the volume averaging method and integrates a thermal model to provide a comprehensive simulation framework. The results of the numerical calculations and experimental measurements show that the model is in good agreement with the experimental data. The predicted discharge capacity of the proposed model is significantly higher than that of the traditional P2D model. This improvement is primarily due to the increased diffusion distance in agglomerates and the non-uniform particle sizes, which result in substantial changes in overpotential, electrolyte concentration, and solid-phase lithium-ion distribution. The model effectively captures the complex electrochemical behavior during discharge, underscoring the importance of considering structural heterogeneities in battery modeling.

Pressure enabled organic reactions via confinement between layers of 2D materials.

Confinement of reactants within nanoscale spaces of low-dimensional materials has been shown to provide reorientation of strained reactants or stabilization of unstable reactants for synthesis of molecules and tuning of chemical reactivity. While few studies have reported chemistry within zero-dimensional pores and one-dimensional nanotubes, organic reactions in confined spaces between two-dimensional materials have yet to be explored. Here, we demonstrate that reactants confined between atomically thin sheets of graphene or hexagonal boron nitride experience pressures as high as 7 gigapascal, which allows the propagation of solvent-free organic reactions that ordinarily do not occur under standard conditions. Specifically, we show that cyclodehydrogenation of hexaphenylbenzene without catalysts as a proof of concept and oxidative polymerization of dopamine into sheet-like crystalline structure are enabled by the effective high pressure experienced by the reactants between the graphene layers. Our results demonstrate a facile, general approach for performing high-pressure chemistry based on confinement of reactants within two-dimensional materials.

Quantum physisorption behavior of methane in nanoporous shales: Model and new mechanism

Methane adsorption in nanoporous shales plays a significant role in the storage and flow of shale gas. Although previously numerous theoretical models have been proposed to describe the gas adsorption behavior, how the potential energy distribution in nanopores impacts gas adsorption remains unclear. The mechanism of methane adsorption in extremely complicated nanopores is still no satisfactory explanation. In this study, a total of 28 shale samples located in the Paleozoic-Mesozoic strata from different sedimentary environments were utilized to investigate the nature and process of quantum physisorption of methane in nanoporous shales. It was suggested that methane confined within nanoscale space shows a quantum effect, and the physisorption behavior of methane may be the result of molecular energy level transition. Further, the quantum physisorption model was developed by considering the quantum potential energy distribution, maximum adsorption amount, gas temperature and gas pressure, which matches the isothermal adsorption data well for a various of shales under widely varied temperature and gas pressure condition. The adsorption amounts of methane with different energy levels can also be obtained by the model. Finally, a new mechanism of the methane quantum physisorption in nanoporous shales was proposed. Uneven spatial distribution of gas molecules and elementary space of gas adsorption are the intrinsic factors of controlling the quantum physisorption behavior. The former is mainly influenced by minimum potential unit (E0) and gas temperature, while the latter is represented by the parameter of maximum adsorption amount (nL) which impacted by specific surface area and gas temperature. Gas pressure only affects the molecule concentration with different energy levels, but does not affect the spatial distribution of molecule. E0 and nL vary in shales from different sedimentary environments, due to the difference in organic matter properties (TOC content and kerogen type), which indirectly impacts the methane physisorption behavior. These results are helpful to deeply understand the storage of methane in shales and improve the efficient development of shale gas. In addition, this study is expected to open a new research direction about the quantum physisorption of gas in nanoporous media.

Cargo quantification of functionalized DNA origami for therapeutic application.

In recent years, notable advances in nanotechnology-based drug delivery have emerged. A particularly promising platform in this field is DNA origami-based nanoparticles, which offer highly programmable surfaces, providing precise control over the nanoscale spacing and stoichiometry of various cargo. These versatile particles are finding diverse applications ranging from basic molecular biology to diagnostics and therapeutics. This growing interest creates the need for effective methods to quantify cargo on DNA origami nanoparticles. Our study consolidates several previously validated methods focusing on gel-based and fluorescence-based techniques, including multiplexed quantification of protein, peptide, and nucleic acid cargo on these nanoparticles. This work may serve as a valuable resource for groups researchers keen on utilizing DNA origami-based nanoparticles in therapeutic applications.

Real Time Tracking of Nanoconfined Water-Assisted Ion Transfer in Functionalized Graphene Derivatives Supercapacitor Electrodes.

Water molecules confined in nanoscale spaces of 2D graphene layers have fascinated researchers worldwide for the past several years, especially in the context of energy storage applications. The water molecules exchanged along with ions during the electrochemical process can aid in wetting and stabilizing the layered materials resulting in an anomalous enhancement in the performance of supercapacitor electrodes. Engineering of 2D carbon electrode materials with various functionalities (oxygen (─O), fluorine (─F), nitrile (─C≡N), carboxylic (─COOH), carbonyl (─C═O), nitrogen (─N)) can alter the ion/water organization in graphene derivatives, and eventually their inherent ion storage ability. Thus, in the current study, a comparative set of functionalized graphene derivatives-fluorine-doped cyanographene (G-F-CN), cyanographene (G-CN), graphene acid (G-COOH), oxidized graphene acid (G-COOH (O)) and nitrogen superdoped graphene (G-N) is systematically evaluated toward charge storage in various aqueous-based electrolyte systems. Differences in functionalization on graphene derivatives influence the electrochemical properties, and the real-time mass exchange during the electrochemical process is monitored by electrochemical quartz crystal microbalance (EQCM). Electrogravimetric assessment revealed that oxidized 2D acid derivatives (G-COOH (O)) are shown to exhibit high ion storage performance along with maximum water transfer during the electrochemical process. The complex understanding of the processes gained during supercapacitor electrode charging in aqueous electrolytes paves the way toward the rational utilization of graphene derivatives in forefront energy storage applications.

Structure and dynamics of amphiphilic patchy cubes in a nanoslit under shear.

Patchy nanocubes are intriguing materials with simple shapes and space-filling and multidirectional bonding properties. Previous studies have revealed various mesoscopic structures such as colloidal crystals in the solid regime and rod-like or fractal-like aggregates in the liquid regime of the phase diagram. Recent studies have also shown that mesoscopic structural properties, such as an average cluster size M and orientational order, in amphiphilic nanocube suspensions are associated with macroscopic viscosity changes, mainly owing to differences in cluster shape among patch arrangements. Although many studies have been conducted on the self-assembled structures of nanocubes in bulk, little is known about their self-assembly in nanoscale spaces or structural changes under shear. In this study, we investigated mixtures of one- and two-patch amphiphilic nanocubes confined in two flat parallel plates at rest and under shear using molecular dynamics simulations coupled with multiparticle collision dynamics. We considered two different patch arrangements for the two-patch particles and two different slit widths H to determine the degree of confinement in constant volume fractions in the liquid regime of the phase diagram. We revealed two unique cluster morphologies that have not been previously observed under bulk conditions. At rest, the size of the rod-like aggregates increased with decreasing H, whereas that of the fractal-like aggregates remained constant. Under weak shear with strong confinement, the rod-like aggregates maintained a larger M than the fractal-like aggregates, which were more rigid and maintained a larger M than the rod-like aggregates under bulk conditions.

Enhanced chemiluminescence resonance energy transfer using surfactant-modified AIE carbon dots.

Chemiluminescence resonance energy transfer (CRET) efficiency can be enhanced by confining CRET donors and acceptors within nanoscale spaces. However, this enhanced efficiency is often affected by uncertainties stemming from the random distribution of CRET donors and acceptors in such confined environments. In this study, a novel confined nanospace was created through the surfactant modification of carbon dots (CDs) exhibiting aggregation-induced emission (AIE) characteristics. Hydrophobic CRET donors could be effectively confined within this nanospace. The distance between the CRET donors and acceptors could be controlled by anchoring the AIE-CDs as the CRET acceptors, resulting in significantly improved CRET efficiency. Furthermore, this AIE-CDs-based CRET system was successfully applied to the detection of hydrogen peroxide (H2O2) in rainwater, showcasing its potential for practical applications.

Dendrite/Volume Expansion-Free Lithium Deposition Inside the Enclosed Nanoscale Space of Electrochemically Modified Graphite

Though over-lithiation of graphite can increase the initial specific capacity of the anodes, the cycling stability is unsatisfactory as metallic lithium depositing on the surface of graphite has poor reversibility. In this work, we utilize electrochemical co-intercalation of Li+ and diethylene glycol dimethyl ether (DEGDME) to prepare [Li-DEGDME]+-graphite co-intercalation compounds ([Li-DEGDME]-Gr) from pristine graphite. The expanded d-spacing and abundant cross-layer voids in the interlayer structure of [Li-DEGDME]-Gr owing to the co-intercalation of [Li-DEGDME]+ complex ions and parasitic chemical reactions between solvent molecules and graphene layers promotes the migration of bare Li+ and provides sufficient interior space for extra lithium-storage. As a result, a much higher lithium-storage capacity of 810 mAh g−1 can be successfully achieved. The extra lithium-storage is proved to originate from the deposition of lithium metal inside the enclosed nanoscale space of the as modified graphite, which inhibits the formation of lithium dendrites, isolates lithium metal from electrolytes and avoids volumetric expansion, enabling the [Li-DEGDME]-Gr electrodes to exhibit better cycling stability with high specific capacity. This work proposes a new strategy to enhance the reversibility of lithium metal plating/stripping by accommodating lithium deposition inside modified carbon materials, thus effectively increasing the reversible capacity of graphite-based anode materials.

Precision nanoscale patterning of TLR ligands for improved cancer immunotherapy

In a recent issue of Nature Nanotechnology, Zeng etal. report that arraying immuno-stimulatory CpG molecules with specific nanoscale spacing on DNA origami nanoparticles enhanced Th1-polarized immune responses. These results highlight spatial presentation of adjuvants as a design strategy to optimize cancer vaccine efficacy, safety, and tolerability.

Fine tuning of CpG spatial distribution with DNA origami for improved cancer vaccination.

Multivalent presentation of ligands often enhances receptor activation and downstream signalling. DNA origami offers a precise nanoscale spacing of ligands, a potentially useful feature for therapeutic nanoparticles. Here we use a square-block DNA origami platform to explore the importance of the spacing of CpG oligonucleotides. CpG engages Toll-like receptors and therefore acts to activate dendritic cells. Through in vitro cell culture studies and in vivo tumour treatment models, we demonstrate that square blocks induce Th1 immune polarization when CpG is spaced at 3.5 nm. We observe that this DNA origami vaccine enhances DC activation, antigen cross-presentation, CD8 T-cell activation, Th1-polarized CD4 activation and natural-killer-cell activation. The vaccine also effectively synergizes with anti-PD-L1 for improved cancer immunotherapy in melanoma and lymphoma models and induces long-term T-cell memory. Our results suggest that DNA origami may serve as a platform for controlling adjuvant spacing and co-delivering antigens in vaccines.

Utilizing multiscale engineered biomaterials to examine TGF-β-mediated myofibroblastic differentiation.

Cells integrate many mechanical and chemical cues to drive cell signalling responses. Because of the complex nature and interdependency of alterations in extracellular matrix (ECM) composition, ligand density, mechanics, and cellular responses it is difficult to tease out individual and combinatorial contributions of these various factors in driving cell behavior in homeostasis and disease. Tuning of material viscous and elastic properties, and ligand densities, in combinatorial fashions would enhance our understanding of how cells process complex signals. For example, it is known that increased ECM mechanics and transforming growth factor beta (TGF-β) receptor (TGF-β-R) spacing/clustering independently drive TGF-β signalling and associated myofibroblastic differentiation. However, it remains unknown how these inputs orthogonally contribute to cellular outcomes. Here, we describe the development of a novel material platform that combines microgel thin films with controllable viscoelastic properties and DNA origami to probe how viscoelastic properties and nanoscale spacing of TGF-β-Rs contribute to TGF-β signalling and myofibroblastic differentiation. We found that highly viscous materials with non-fixed TGF-β-R spacing promoted increased TGF-β signalling and myofibroblastic differentiation. This is likely due to the ability of cells to better cluster receptors on these surfaces. These results provide insight into the contribution of substrate properties and receptor localisation on downstream signalling. Future studies allow for exploration into other receptor-mediated processes.

Quantitative analysis of molecular transport in the extracellular space using physics-informed neural network

The brain extracellular space (ECS), an irregular, extremely tortuous nanoscale space located between cells or between cells and blood vessels, is crucial for nerve cell survival. It plays a pivotal role in high-level brain functions such as memory, emotion, and sensation. However, the specific form of molecular transport within the ECS remain elusive. To address this challenge, this paper proposes a novel approach to quantitatively analyze the molecular transport within the ECS by solving an inverse problem derived from the advection-diffusion equation (ADE) using a physics-informed neural network (PINN). PINN provides a streamlined solution to the ADE without the need for intricate mathematical formulations or grid settings. Additionally, the optimization of PINN facilitates the automatic computation of the diffusion coefficient governing long-term molecule transport and the velocity of molecules driven by advection. Consequently, the proposed method allows for the quantitative analysis and identification of the specific pattern of molecular transport within the ECS through the calculation of the Péclet number. Experimental validation on two datasets of magnetic resonance images (MRIs) captured at different time points showcases the effectiveness of the proposed method. Notably, our simulations reveal identical molecular transport patterns between datasets representing rats with tracer injected into the same brain region. These findings highlight the potential of PINN as a promising tool for comprehensively exploring molecular transport within the ECS.

Surface-Patterned DNA Origami Rulers Reveal Nanoscale Distance Dependency of the Epidermal Growth Factor Receptor Activation.

The nanoscale arrangement of ligands can have a major effect on the activation of membrane receptor proteins and thus cellular communication mechanisms. Here we report on the technological development and use of tailored DNA origami-based molecular rulers to fabricate "Multiscale Origami Structures As Interface for Cells" (MOSAIC), to enable the systematic investigation of the effect of the nanoscale spacing of epidermal growth factor (EGF) ligands on the activation of the EGF receptor (EGFR). MOSAIC-based analyses revealed that EGF distances of about 30-40 nm led to the highest response in EGFR activation of adherent MCF7 and Hela cells. Our study emphasizes the significance of DNA-based platforms for the detailed investigation of the molecular mechanisms of cellular signaling cascades.

Unravelling Twin Topotactic/Nontopotactic Reactive TiSe2 Cathodes for Aqueous Batteries.

Titanium selenide (TiSe2 ), a model transition metal chalcogenide material, typically relies on topotactic ion intercalation/deintercalation to achieve stable ion storage with minimal disruption of the transport pathways but has restricted capacity (<130 mAh g-1 ). Developing novel energy storage mechanisms beyond conventional intercalation to break capacity limits in TiSe2 cathodes is essential yet challenging. Herein, the ion storage properties of TiSe2 are revisited and an unusual thermodynamically stable twin topotactic/nontopotactic Cu2+ accommodation mechanism for aqueous batteries is unraveled. In situ synchrotron X-ray diffraction and ex situ microscopy jointly demonstrated that topotactic intercalation sustained the ion transport framework, nontopotactic conversion involved localized multielectron reactions, and these two parallel reactions are miraculously intertwined in nanoscale space. Comprehensive experimental and theoretical results suggested that the twin-reaction mechanism significantly improved the electron transfer ability, and the reserved intercalated TiSe2 structure anchored the reduced titanium monomers with high affinity and promoted efficient charge transfer to synergistically enhance the capacity and reversibility. Consequently, TiSe2 nanoflake cathodes delivered a never-before-achieved capacity of 275.9 mAh g-1 at 0.1 A g-1 , 93.5% capacity retention over 1000 cycles, and endow hybrid batteries (TiSe2 -Cu||Zn) with a stable energy supply of 181.34Wh kg-1 at 2339.81W kg-1 , offering a promising model for aqueous ion storage.

Nanojunctions: Specificity of Ca2+ signaling requires nano-scale architecture of intracellular membrane contact sites

Spatio-temporal definition of Ca2+ signals involves the assembly of signaling complexes within the nano-architecture of contact sites between the sarco/endoplasmic reticulum (SR/ER) and the plasma membrane (PM). While the requirement of precise spatial assembly and positioning of the junctional signaling elements is well documented, the role of the nano-scale membrane architecture itself, as an ion-reflecting confinement of the signalling unit, remains as yet elusive. Utilizing the Na+/Ca2+ Exchanger-1 / SR/ER Ca2+ ATPase-2-mediated ER Ca2+ refilling process as a junctional signalling paradigm, we provide here the first evidence for an indispensable cellular function of the junctional membrane architecture. Our stochastic modeling approach demonstrates that junctional ER Ca2+ refilling operates exclusively at nano-scale membrane spacing, with a strong inverse relationship between junctional width and signaling efficiency. Our model predicts a breakdown of junctional Ca2+ signaling with loss of reflecting membrane confinement. In addition we consider interactions between Ca2+ and the phospholipid membrane surface, which may support interfacial Ca2+ transport and promote receptor targeting. Alterations in the molecular and nano-scale membrane organization at organelle-PM contacts are suggested as a new concept in pathophysiology.

Electrochemical carbon–carbon coupling with enhanced activity and racemate stereoselectivity by microenvironment regulation

Enzymes are characteristic of catalytic efficiency and specificity by maneuvering multiple components in concert at a confined nanoscale space. However, achieving such a configuration in artificial catalysts remains challenging. Herein, we report a microenvironment regulation strategy by modifying carbon paper with hexadecyltrimethylammonium cations, delivering electrochemical carbon–carbon coupling of benzaldehyde with enhanced activity and racemate stereoselectivity. The modified electrode–electrolyte interface creates an optimal microenvironment for electrocatalysis—it engenders dipolar interaction with the reaction intermediate, giving a 2.2-fold higher reaction rate (from 0.13 to 0.28 mmol h−1 cm−2); Moreover, it repels interfacial water and modulates the conformational specificity of reaction intermediate by facilitating intermolecular hydrogen bonding, affording 2.5-fold higher diastereomeric ratio of racemate to mesomer (from 0.73 to 1.82). We expect that the microenvironment regulation strategy will lead to the advanced design of electrode–electrolyte interface for enhanced activity and (stereo)selectivity that mimics enzymes.