Engineering the Cellular Microenvironment: Integrating Three-Dimensional Nontopographical and Two-Dimensional Biochemical Cues for Precise Control of Cellular Behavior.

The development of biomaterials capable of regulating cellular processes and guiding cell fate decisions has broad implications in tissue engineering, regenerative medicine, and cell-based assays for drug development and disease modeling. Recent studies have shown that three-dimensional (3D) nanoscale physical cues such as nanotopography can modulate various cellular processes like adhesion and endocytosis by inducing nanoscale curvature on the plasma and nuclear membranes. Two-dimensional (2D) biochemical cues such as protein micropatterns can also regulate cell function and fate by controlling cellular geometries. Development of biomaterials with precise control over nanoscale physical and biochemical cues can significantly influence programming cell function and fate. In this study, we utilized a laser-assisted micropatterning technique to manipulate the 2D architectures of cells on 3D nanopillar platforms. We performed a comprehensive analysis of cellular and nuclear morphology and deformation on both nanopillar and flat substrates. Our findings demonstrate the precise engineering of single cell architectures through 2D micropatterning on nanopillar platforms. We show that the coupling between the nuclear and cell shape is disrupted on nanopillar surfaces compared to flat surfaces. Furthermore, our results suggest that cell elongation on nanopillars enhances nanopillar-induced endocytosis. We believe our platform serves as a versatile tool for further explorations into programming cell function and fate through combined physical cues that create nanoscale curvature on cell membranes and biochemical cues that control the geometry of the cell.

In Situ Tracking of Water Oxidation Generated Nanoscale Dynamics in Layered Double Hydroxides Nanosheets.

Layered double hydroxides (LDHs) are potential catalysts for water oxidation, and it is recognized that they undergo dynamic evolution during the operation. However, little is known about the interfacial behaviors at the nanoscale under working conditions nor the underlying effects on electrocatalytic performance. Herein, using electrochemical atomic force microscopy, we in situ visualize the heterogeneous evolution of LDH nanosheets during oxygen evolution reaction (OER). By further combining density functional theory calculations, we elucidate the origin of the heterogeneous dynamics and their impact on the OER efficiency. Our findings demonstrate that NiCo LDHs transform to the catalytically active NiCoOx(OH)2-x phase during OER, and the redox transition between is accompanied by compressive and tensile strain, leading to in-plane contraction and reversible expansion of the nanosheets. Nonisotropic strain and out-of-plane strain relaxation due to defects and interparticle interactions result in cracking and wrinkling in the nanostructure, which is responsible for the partial activation and long-term deterioration of LDH electrocatalysts toward the OER. With this knowledge, we suggest and validate that engineering defects can precisely tune these dynamic behaviors, improving the OER activity and stability among LDH-based electrocatalysts.

Non-fibril amyloid aggregation at the air/water interface: self-adaptive pathway resulting in a 2D Janus nanofilm.

The amyloid states of proteins are implicated in several neurodegenerative diseases and bioadhesion processes. However, the classical amyloid fibrillization mechanism fails to adequately explain the formation of polymorphic aggregates and their adhesion to various surfaces. Herein, we report a non-fibril amyloid aggregation pathway, with disulfide-bond-reduced lysozyme (R-Lyz) as a model protein under quasi-physiological conditions. Very different from classical fibrillization, this pathway begins with the air-water interface (AWI) accelerated oligomerization of unfolded full-length protein, resulting in unique plate-like oligomers with self-adaptive ability, which can adjust their conformations to match various interfaces such as the asymmetric AWI and amyloid-protein film surface. The pathway enables a stepwise packing of the plate-like oligomers into a 2D Janus nanofilm, exhibiting a divergent distribution of hydrophilic/hydrophobic residues on opposite sides of the nanofilm. The resulting Janus nanofilm possesses a top-level Young's modulus (8.3 ± 0.6 GPa) among amyloid-based materials and exhibits adhesive strength two times higher (145 ± 81 kPa) than that of barnacle cement. Furthermore, we found that such an interface-directed pathway exists in several amyloidogenic proteins with a similar self-adaptive 2D-aggregation process, including bovine serum albumin, insulin, fibrinogen, hemoglobin, lactoferrin, and ovalbumin. Thus, our findings on the non-fibril self-adaptive mechanism for amyloid aggregation may shed light on polymorphic amyloid assembly and their adhesions through an alternative pathway.

Chitosan Composite Membrane with Efficient Hydroxide Ion Transport via Nano-Confined Hydrogen Bonding Network for Alkaline Zinc-Based Flow Batteries.

The development of membranes with rapid and selective ionic transport is imperative for diverse electrochemical energy conversion and storage systems, including fuel cells and flow batteries. However, the practical application of membranes is significantly hindered by their limited conductivity and stability under strong alkaline conditions. Herein, a unique composite membrane decorated with functional Cu2+ cross-linked chitosan (Cts-Cu-M) is reported and their high hydroxide ion conductivity and stability in alkaline flow batteries are demonstrated. The underlying hydroxide ions transport of the membrane through Cu2+ coordinated nano-confined channels with abundant hydrogen bonding network via Grotthuss (proton hopping) mechanism is proposed. Consequently, the Cts-Cu-M membrane achieves high hydroxide ion conductivity with an area resistance of 0.17 Ω cm2 and enables an alkaline zinc-based flow battery to operate at 320 mA cm-2, along with an energy efficiency of ≈80%. Furthermore, the membrane enables the battery for 200 cycles of long-cycle stability at a current density of 200 mA cm-2. This study offers an in-depth understanding of ion transport for the design and preparation of high-performance membranes for energy storage devices and beyond.

Recent advances in two-dimensional nanomaterials for sustainable wearable electronic devices.

The widespread adoption of smart terminals has significantly boosted the market potential for wearable electronic devices. Two-dimensional (2D) nanomaterials show great promise for flexible, wearable electronics of next-generation electronic materials and have potential in energy, optoelectronics, and electronics. First, this review focuses on the importance of functionalization/defects in 2D nanomaterials, a discussion of different kinds of 2D materials for wearable devices, and the overall structure-property relationship of 2D materials. Then, in this comprehensive review, we delve into the burgeoning realm of emerging applications for 2D nanomaterial-based flexible wearable electronics, spanning diverse domains such as energy, medical health, and displays. A meticulous exploration is presented, elucidating the intricate processes involved in tailoring material properties for specific applications. Each research direction is dissected, offering insightful perspectives and dialectical evaluations that illuminate future trajectories and inspire fruitful investigations in this rapidly evolving field.

Insight into the hydration friction of lipid bilayers.

Hydration layers formed on charged sites play crucial roles in many hydration lubrication systems in aqueous media. However, the underlying molecular mechanism is not well understood. Herein, we explored the hydration friction of lipid bilayers with different charged headgroups at the nanoscale through a combination of frequency-modulation atomic force microscopy and friction force microscopy. The nanoscale friction experiments showed that the hydration friction coefficient and frictional energy dissipation of a cationic lipid (DPTAP) were much lower than those of zwitterionic (DPPE) and anionic (DPPG) lipids. The hydration layer probing at the surfaces of different lipid bilayers clearly revealed the relationship between the charged lipid headgroups and hydration layer structures. Our detailed analysis demonstrated that the cationic lipid had the largest hydration force in comparison with zwitterionic and anionic lipids. These friction and hydration force results indicated that the difference of the lipid headgroup charge resulted in different hydration strengths which led to the difference of hydration friction behaviors. The findings in this study provide molecular insights into the hydration friction of lipid bilayers, which has potential implications for the development of efficient hydration lubrication systems with boundary lipid bilayers in aqueous media.

Phospholipid Epitaxial Assembly Behavior on a Hydrophobic Highly Ordered Pyrolytic Graphite Surface.

Supported lipid bilayers (SLBs) are excellent models of cell membranes. However, most SLBs exist in the form of phospholipid molecules standing on a substrate, making it difficult to have a side view of the phospholipid membranes. In this study, the phospholipid striped lamella with the arrangement of their alkane tails lying on highly ordered pyrolytic graphite (HOPG) was constructed by a spin coating method. Atomic force microscopy and molecular dynamics simulations are utilized to study the self-assembly of phospholipids on HOPG. Results show that various phospholipids with different packing parameters and electrical property are able to epitaxially adsorb on HOPG. 0.1 mg/mL Plasm PC (0.1 mg/mL) could form a striped monolayer with a width of 5.93 ± 0.21 nm and form relatively stable four striped layers with the concentration increasing to 1 mg/mL. The width of the DOPS multilayer is more than that of electroneutral lipids due to the static electrical repulsion force. This universal strategy sheds light on direct observation of the membrane structure from the side view and modification of 2D materials with amphiphilic biomolecules.

Aggregation-induced signal amplification strategy based on peptide self-assembly for ultrasensitive electrochemical detection of melanoma biomarker.

The detection of melanoma circulating biomarker in liquid biopsies is current under evaluation for being potentially utilized for earlier cancer diagnosis and its metastasis. Herein, we developed a non-invasive electrochemical approach for ultrasensitive detection of the S100B, serving as a potential promising blood circulating biomarker of melanoma, based on an aggregation-induced signal amplification (AISA) strategy via in-situ peptide self-assembly. The fundamental principle of this assay is that the designed amphiphilic peptides (C16-Pep-Fc), fulfilling multiple functions, feature both a recognition region for specific binding to S100B and an aggregation (self-assembly) region for the formation of peptide nanomicelles under mild conditions. The C16 tails were encapsulated within the hydrophobic core of the aggregates, while the relatively hydrophilic recognition fragment Pep and Fc tag were exposed on the outer surface for subsequent recognition of S100B and signal output. AISA provided remarkable accumulation of electroactive Fc moieties that enabled ultrasensitive S100B detection of as low as 0.02 nM, which was 10-fold lower than un-amplified approach and better than previously reported assays. As a proof-of-concept study, further experiments also highlighted the good reproducibility and stability of AISA and demonstrated its usability when applied to simulated serum samples. Hence, this work not only presented a valuable assay tool for ultrasensitive detecting protein biomarker, but also advocated for the utilization of aggregation-induced signal amplification in electrochemical biosensing system, given its considerable potential for future practical applications.

Universality of Hair as a Nucleant: Exploring the Effects of Surface Chemistry and Topography.

The ability to control crystal nucleation through the simple addition of a nucleating agent (nucleant) is desirable for a huge range of applications. However, effective nucleating agents are known for only a small number of systems, and many questions remain about the mechanisms by which they operate. Here, we explore the features that make an effective nucleant and demonstrate that the biological material hair-which naturally possesses a chemically and topographically complex surface structure-has excellent potential as an effective nucleating agent. Crystallization of poorly soluble compounds in the presence of hairs from a range of mammals shows that nucleation preferentially occurs at the cuticle step edges, while a novel microdroplet-based methodology was used to quantify the nucleating activities of different hairs. This showed that the activities of the hairs can be tuned over a wide range using chemical treatments. Analysis of the hair structure and composition using atomic force microscopy, scanning ion conductance microscopy, and X-ray photoelectron spectroscopy demonstrates that surface chemistry, surface topography, and surface charge all act in combination to create effective nucleation sites. This work therefore contributes to our understanding of heterogeneous nucleating agents and shows that surface topography as well as surface chemistry can be used in the design or selection of universal nucleating agents.

Elevated concentrations cause upright alpha-synuclein conformation at lipid interfaces.

The amyloid aggregation of α-synuclein (αS), related to Parkinson's disease, can be catalyzed by lipid membranes. Despite the importance of lipid surfaces, the 3D-structure and orientation of lipid-bound αS is still not known in detail. Here, we report interface-specific vibrational sum-frequency generation (VSFG) experiments that reveal how monomeric αS binds to an anionic lipid interface over a large range of αS-lipid ratios. To interpret the experimental data, we present a frame-selection method ("ViscaSelect") in which out-of-equilibrium molecular dynamics simulations are used to generate structural hypotheses that are compared to experimental amide-I spectra via excitonic spectral calculations. At low and physiological αS concentrations, we derive flat-lying helical structures as previously reported. However, at elevated and potentially disease-related concentrations, a transition to interface-protruding αS structures occurs. Such an upright conformation promotes lateral interactions between αS monomers and may explain how lipid membranes catalyze the formation of αS amyloids at elevated protein concentrations.

Identification of hybrid amyloid strains assembled from amyloid-ßand human islet amyloid polypeptide.

Cross-fibrillation of amyloid-ß(Aß) peptides and human islet amyloid polypeptides (hIAPP) has revealed a close correlation between Alzheimer's disease and type 2 diabetes (T2D). Importantly, different amyloid strains are likely to lead to the clinical pathological heterogeneity of degenerative diseases due to toxicity. However, given the complicated cross-interactions between different amyloid peptides, it is still challenging to identify the polymorphism of the hybrid amyloid strains and reveal mechanistic insights into aggregation, but highly anticipated due to their significance. In this study, we investigated the cross-fibrillation of Aßpeptides and different hIAPP species (monomers, oligomers, and fibrils) using combined experimental and simulation approaches. Cross-seeding and propagation of different amyloid peptides monitored by experimental techniques proved that the three species of hIAPP aggregates have successively enhanced Aßfibrillation, especially for hIAPP fibrils. Moreover, the polymorphism of these morphologically similar hybrid amyloid strains could be distinguished by testing their mechanical properties using quantitative nanomechanical mapping, where the assemblies of Aß-hIAPP fibrils exhibited the high Young's modulus. Furthermore, the enhanced internal molecular interactions andß-sheet structural transformation were proved by exploring the conformational ensembles of Aß-hIAPP heterodimer and Aß-hIAPP decamer using molecular dynamic simulations. Our findings pave the way for identifying different hybrid amyloid strains by quantitative nanomechanical mapping and molecular dynamic simulations, which is important not only for the precise classification of neurodegenerative disease subtypes but also for future molecular diagnosis and therapeutic treatment of multiple interrelated degenerative diseases.

Amyloid-like nanofibrous network confined and aligned ultrafine bimetallic nanozymes for smart antibacterial therapy.

Nanozyme-based antibacterial therapy (NABT) has emerged as a promising strategy to combat bacterial antimicrobial resistance. Engineering the noble metal nanozymes with strong bacterial capture and high catalytic activity for enhanced NABT is highly anticipated but still challenged. Herein, we developed hybrid nanozymes by engineering ultrafine bimetallic Au/Cu nanoparticles confined on the lysozyme amyloid-like nanofibrous networks (LNF). The introduction of copper in the nanozymes facilitates the H2O2 adsorption and reduces the energy barrier for activating the H2O2 decomposition to form •OH, meanwhile displaying the significantly enhanced POD-like activity under NIR irradiation. Taking advantage of the inherent supramolecular networks inspired from human defensin 6-trapping bacteria mechanism, the hybrid nanozymes effectively capture the bacteria and allow the catalytic attack around the bacterial surfaces to improve the antibacterial efficiency. Finally, the as-prepared nanozymes exhibit the preeminent bactericidal efficacy against bacteria, especially for drug-resistant bacteria both in vitro and in vivo, and the effect on wound healing.

In-situ PLL-g-PEG Functionalized Nanopore for Enhancing Protein Characterization.

Single-molecule nanopore detection technology has revolutionized proteomics research by enabling highly sensitive and label-free detection of individual proteins. Herein, we designed a small, portable, and leak-free flowcell made of PMMA for nanopore experiments. In addition, we developed an in situ functionalizing PLL-g-PEG approach to produce non-sticky nanopores for measuring the volume of diseases-relevant biomarker, such as the Alpha-1 antitrypsin (AAT) protein. The in situ functionalization method allows continuous monitoring, ensuring adequate functionalization, which can be directly used for translocation experiments. The functionalized nanopores exhibit improved characteristics, including an increased nanopore lifetime and enhanced translocation events of the AAT proteins. Furthermore, we demonstrated the reduction in the translocation event's dwell time, along with an increase in current blockade amplitudes and translocation numbers under different voltage stimuli. The study also successfully measures the single AAT protein volume (253 nm3 ), which closely aligns with the previously reported hydrodynamic volume. The real-time in situ PLL-g-PEG functionalizing method and the developed nanopore flowcell hold great promise for various nanopores applications involving non-sticky single-molecule characterization.

Folding Double-Stranded DNA into Designed Shapes with Triplex-Forming Oligonucleotides.

The compaction and organization of genomic DNA is a central mechanism in eukaryotic cells, but engineered architectural control over double-stranded DNA (dsDNA) is notably challenging. Here, long dsDNA templates are folded into designed shapes via triplex-mediated self-assembly. Triplex-forming oligonucleotides (TFOs) bind purines in dsDNA via normal or reverse Hoogsteen interactions. In the triplex origami methodology, these non-canonical interactions are programmed to compact dsDNA (linear or plasmid) into well-defined objects, which demonstrate a variety of structural features: hollow and raster-filled, single- and multi-layered, with custom curvatures and geometries, and featuring lattice-free, square-, or honeycomb-pleated internal arrangements. Surprisingly, the length of integrated and free-standing dsDNA loops can be modulated with near-perfect efficiency; from hundreds down to only six bp (2 nm). The inherent rigidity of dsDNA promotes structural robustness and non-periodic structures of almost 25.000 nt are therefore formed with fewer unique starting materials, compared to other DNA-based self-assembly methods. Densely triplexed structures also resist degradation by DNase I. Triplex-mediated dsDNA folding is methodologically straightforward and orthogonal to Watson-Crick-based methods. Moreover, it enables unprecedented spatial control over dsDNA templates.

Tannic acid-functionalized 3D porous nanofiber sponge for antibiotic-free wound healing with enhanced hemostasis, antibacterial, and antioxidant properties.

Developing an antibiotic-free wound dressing with effective hemostasis and antibacterial and antioxidant capacity is highly desirable. In this work, a three-dimensional (3D) chitosan/polyvinyl alcohol-tannic acid porous nanofiber sponge (3D-TA) was prepared via electrospinning. Compared with two-dimensional (2D) fiber membrane, the unique fluffy 3D-TA nanofiber sponge had high porosity, water absorption and retention ability, hemostatic capacity. Furthermore, the 3D sponge functionalized by tannic acid (TA) endow the sponge with high antibacterial and antioxidant capacity without loading antibiotics. In addition, 3D-TA composite sponges have shown highly biocompatibility against L929 cells. The in vivo experiment shows the 3D-TA is enable to accelerate wound healing. This newly 3D-TA sponges hold great potential as wound dressings for future clinical application.

Liquid-Phase Friction of Two-Dimensional Molybdenum Disulfide at the Atomic Scale.

Tribological properties depend strongly on environmental conditions such as temperature, humidity, and operation liquid. However, the origin of the liquid effect on friction remains largely unexplored. Herein, taking molybdenum disulfide (MoS2) as a model system, we explored the nanoscale friction of MoS2 in polar (water) and nonpolar (dodecane) liquids through friction force microscopy. The friction force exhibits a similar layer-dependent behavior in liquids as in air; i.e., thinner samples have a larger friction force. Interestingly, friction is significantly influenced by the polarity of the liquid, and it is larger in polar water than in nonpolar dodecane. Atomically resolved friction images together with atomistic simulations reveal that the polarity of the liquid has a substantial effect on friction behavior, where liquid molecule arrangement and hydrogen-bond formation lead to a higher resistance in polar water in comparison to that in nonpolar dodecane. This work provides insights into the friction on two-dimensional layered materials in liquids and holds great promise for future low-friction technologies.

Fluorescent probe for highly selective detection of cysteine in living cells.

Cys play an important physiological role in the human body. Abnormal Cys concentration can cause many diseases. Therefore, it is of great significance to detect Cys with high selectivity and sensitivity in vivo. Because homocysteine (Hcy) and glutathione (GSH) have similar reactivity and structure to cysteine, few fluorescent probes have been reported to be specific and efficient for cysteine. In this study, we designed and synthesized an organic small molecule fluorescent probe ZHJ-X based on cyanobiphenyl, which can be used to specifically recognize cysteine. The probe ZHJ-X exhibits specific selectivity for cysteine, high sensitivity, short reaction response time, good anti-interference ability, and has a low detection limit of 3.8 × 10-6 M. The probe ZHJ-X was successfully applied to the visualization of Cys in living cells and had great application prospects in cell imaging and detection.

Injectable 2D flexible hydrogel sheets for optoelectrical/biochemical dual stimulation of neurons.

Major challenges in developing implanted neural stimulation devices are the invasiveness, complexity, and cost of the implantation procedure. Here, we report an injectable, nanofibrous 2D flexible hydrogel sheet-based neural stimulation device that can be non-invasively implanted via syringe injection for optoelectrical and biochemical dual stimulation of neuron. Specifically, methacrylated gelatin (GelMA)/alginate hydrogel nanofibers were mechanically reinforced with a poly(lactide-co-ε-caprolactone) (PLCL) core by coaxial electrospinning. The lubricant hydrogel shell enabled not only injectability, but also facile incorporation of functional nanomaterials and bioactives. The nanofibers loaded with photocatatlytic g-C3N4/GO nanoparticles were capable of stimulating neural cells via blue light, with a significant 36.3 % enhancement in neurite extension. Meanwhile, the nerve growth factor (NGF) loaded nanofibers supported a sustained release of NGF with well-maintained function to biochemically stimulate neural differentiation. We have demonstrated the capability of an injectable, hydrogel nanofibrous, neural stimulation system to support neural stimulation both optoelectrically and biochemically, which represents crucial early steps in a larger effort to create a minimally invasive system for neural stimulation.

Emerging MoS2 Wafer-Scale Technique for Integrated Circuits.

As an outstanding representative of layered materials, molybdenum disulfide (MoS2) has excellent physical properties, such as high carrier mobility, stability, and abundance on earth. Moreover, its reasonable band gap and microelectronic compatible fabrication characteristics makes it the most promising candidate in future advanced integrated circuits such as logical electronics, flexible electronics, and focal-plane photodetector. However, to realize the all-aspects application of MoS2, the research on obtaining high-quality and large-area films need to be continuously explored to promote its industrialization. Although the MoS2 grain size has already improved from several micrometers to sub-millimeters, the high-quality growth of wafer-scale MoS2 is still of great challenge. Herein, this review mainly focuses on the evolution of MoS2 by including chemical vapor deposition, metal-organic chemical vapor deposition, physical vapor deposition, and thermal conversion technology methods. The state-of-the-art research on the growth and optimization mechanism, including nucleation, orientation, grain, and defect engineering, is systematically summarized. Then, this review summarizes the wafer-scale application of MoS2 in a transistor, inverter, electronics, and photodetectors. Finally, the current challenges and future perspectives are outlined for the wafer-scale growth and application of MoS2.

Ion-mediated control of structural integrity and reconfigurability of DNA nanostructures.

Nucleic acid-based biomolecular self-assembly enables the creation of versatile functional architectures. Electrostatic screening of the negative charges of nucleic acids is essential for their folding and stability; thus, ions play a critical role in nucleic acid self-assembly in both biology and nanotechnology. However, the ion-DNA interplay and the resulting ion-specific structural integrity and responsiveness of DNA constructs are underexploited. Here, we harness a wide range of mono- and divalent ions to control the structural features of DNA origami constructs. Using atomic force microscopy and Förster resonance energy transfer (FRET) spectroscopy down to the single-molecule level, we report on the global and local structural performance and responsiveness of DNA origami constructs following self-assembly, upon post-assembly ion exchange and post-assembly ion-mediated reconfiguration. We determined the conditions for highly efficient DNA origami folding in the presence of several mono- (Li+, Na+, K+, Cs+) and divalent (Ca2+, Sr2+, Ba2+) ions, expanding the range where DNA origami structures can be exploited for custom-specific applications. We then manipulated fully folded constructs by exposing them to unfavorable ionic conditions that led to the emergence of substantial disintegrity but not to unfolding. Moreover, we found that poorly assembled nanostructures at low ion concentrations undergo substantial self-repair upon ion addition in the absence of free staple strands. This reconfigurability occurs in an ion type- and concentration-specific manner. Our findings provide a fundamental understanding of the ion-mediated structural responsiveness of DNA origami at the nanoscale enabling applications under a wide range of ionic conditions.