Bacterial biofilms are organized microbial communities that profoundly impact medicine, industry, and microbial ecology. Biofilm formation begins with nanoscale adhesion events between single bacteria and a surface, and the earliest stages of surface colonization involve reversible interactions that transition to irreversible attachment through the secretion of specialized nanoscale bioadhesins. Understanding and controlling the initial interactions between adhesin and surface is key to control and prevent biofilm formation. Here, we investigate the nanoscale adhesion dynamics of single Caulobacter crescentus cells, a dominant early colonizer in environmental biofouling, focusing on its holdfast, a strong nanoscale adhesive organelle that mediates irreversible attachment within seconds of contact. To characterize the time-dependent mechanical properties of holdfast, we developed the Trapezoid, a custom optical tweezers platform that combines nanometer spatial precision with millisecond temporal control of cell position, contact timing, and applied force on defined surfaces. We implemented a trapezoidal temporal profile of these programmed contact cycles, in which a single cell is brought into contact with the surface, maintained for a defined duration, retracted, and subjected to controlled pulling forces. This approach enables real-time quantification of nanoscale adhesion onset, holdfast deployment kinetics, and influence of surface chemistry at the level of individual live adhesion events. Our results dissect the physical and biochemical determinants of bacterial adhesion, providing a quantitative framework for the rational design of antiadhesive coatings, nanoscale biofouling control strategies, and bioinspired adhesives functional in wet environments.
Phase transitions are omnipresent in modern condensed matter physics and its applications. In solids, first-order phase transformations typically occur by nucleation and growth under nonequilibrium conditions. Under constant external conditions, e.g., constant annealing temperature and pressure, the nucleation and growth dynamics are often thought of as spatially and temporally independent. Here, in situ Bragg X-ray photon correlation spectroscopy (XPCS) reveals nanoscale spatial and dynamical heterogeneity in the perovskite-to-brownmillerite topotactic phase transformation in La0.7Sr0.3CoO3 thin films annealed under constant reducing conditions over a time span of multiple hours. Specifically, a time scale associated with domain growth remains stable, with a corresponding domain wall speed of vd = 6 ± 0.5 × 10-4 nm/s (2 ± 0.2 nm/h), while a slower time scale, associated with temperature-driven depinning of domains, leads to accelerating dynamics with time scales following an aging power law with exponent -2.2 ± 0.5. This experiment demonstrates that Bragg XPCS is a powerful tool to study nanoscale dynamics in structural phase transformations, with the ability to extract quantitative average values related to nanodomain motion in situ. The results are relevant for phase engineering of phase-change devices, as they show that nanoscale dynamics, linked to domain and domain-wall motion, can continuously evolve and speed up with time, even hours after the initiation of the phase transformation, with potential repercussions on electrical performance.
Many viruses have evolved remarkably intricate polyhedral shells capable of undergoing symmetric transformations in response to external stimuli to initiate payload release. So far, such deployable auxetic nanostructures are not available in the synthetic realm. Here we present a nanoscale Jitterbug transformer realized by a DNA origami structure that can reconfigure its conformation upon chemical and optical signals while maintaining a Poisson's ratio of -1. By combining mechanical design principles with molecular dynamics simulations, we design the DNA Jitterbug to form a compact octahedron that stores elastic energy and spontaneously transitions into an expanded cuboctahedron by releasing it. DNA transformers are demonstrated to act similar to viruses that can create nanopores on lipid membranes and regulate payload release into vesicles. Integrating programmable DNA self-assembly with free-energy-guided mechanical design, this work provides a pathway toward adaptive nanomaterials with potential in synthetic organelles and stimuli-responsive nanodevices.
Hepatocellular carcinoma (HCC) remains a leading driver of cancer-related mortality, characterized by profound heterogeneity and a formidable Tumor microenvironment (TME). Conventional therapeutic interventions, including traditional chemotherapy and targeted small molecules, are frequently hindered by critical limitations such as poor aqueous solubility, rapid metabolic clearance, severe systemic toxicity, and the rapid onset of multidrug resistance. Furthermore, these free therapeutic agents struggle to penetrate the dense hepatic stroma. Nanoscale drug delivery systems (NDDS) have emerged as a transformative paradigm to overcome these intractable bottlenecks. By leveraging size-mediated passive accumulation, active ligand recognition, and intelligent microenvironment-responsive designs, nanocarriers can significantly prolong systemic circulation, facilitate deep tumor penetration, and achieve spatiotemporally controlled payload release. This review provides a comprehensive and critical analysis of the evolving landscape of HCC nanomedicine. We systematically evaluate the delivery mechanisms and pharmacokinetics of phytochemicals, synthetic molecules, and advanced gene therapeutic modules (RNAi and CRISPR/Cas9). Furthermore, we provide a comparative evaluation of sustainable "green" biomaterials against traditional carriers, detail sophisticated surface functionalization strategies that range from ranging from ligand-mediated targeting to cell-membrane biomimetic "stealth" coatings and explore multi-stimuli responsive platforms. Finally, we critically discuss current clinical translational bottlenecks, including protein corona formation, immunogenicity, and scalable manufacturing, thereby offering a strategic roadmap for the clinical realization of next-generation hepatic nanotherapeutics.
In this study, an electrical spark discharge method was used under ambient temperature and pressure conditions to prepare magnesium hydroxide nanocolloids. The entire preparation procedure was conducted in DW to ensure that the manufacturing environment does not cause airborne nanoparticle dispersion. Two colloid preparation experiments were conducted by adjusting the parameters of peak current (IP) and pulse cycle time (T P). The results indicated that among all samples, the sample prepared with IP6 and T P set to 70-70 μs exhibited the most favorable colloidal properties. Ultraviolet-visible spectrometry revealed a strong UV absorption peak at 192 nm, an absorbance value of 2.589, and zeta potential measurements showed a value of 35.2 mV. Transmission electron microscopy analysis indicated that the smallest particle size in the colloid was approximately 36.921 nm, with an almost spherical morphology, and that the lattice width of the particles was 0.237 nm.
As atomic-scale archetypes for multi-electron transfer, iron-sulfur clusters are compelling candidates for the design of redox-active, catalytic nanomaterials; yet, translating their enzymatic proficiency into robust synthetic platforms remains a challenge. A key bottleneck lies in replicating the outer-sphere environment, which modulates the cluster's electronic landscape, provides site-isolation, and facilitates catalytic pathways via programmable noncovalent interactions. Herein, we demonstrate a host-guest strategy for systematically tuning iron-sulfur cofactor models within tetrahedral [M4L6]8+ cages (M = Ni, Fe, Zn). Successful encapsulation of [Fe4S4(SR)4]2- (R = Ph, ─CH2CH2OH) was confirmed by 1D/2D NMR spectroscopy and ESI mass spectrometry, while titration studies confirmed association constants (Ka) > 107 m-1. Spectroscopic characterization by 57Fe Mössbauer, X-ray photoelectron, IR, and UV-vis spectroscopy reveals significant shifts in Fe─S bond covalency and electron density that converge toward those of the native, protein-bound cofactors. Control studies with [Fe4S4(StBu)4]2-, which associates with the host primarily through outer-sphere ion pairing, demonstrate that while the electrostatic field generated by the framework's corner vertices is a primary driver of these electronic perturbations, internal confinement effects such as π-π stacking and hydrogen bonding provide important secondary modulations. This work establishes a foundation for utilizing cage-stabilized cofactors in the development of sophisticated, energy-efficient catalytic systems.
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The ryanodine receptor (RyR2) is an intracellular Ca2+ release channel which mediates numerous cellular functions across different tissues. Dysregulation of RyR2 channel activity leads to pathological Ca2+ release, which often underlies disrupted cellular signaling in disease states. In the heart, RyR2 channels forms discrete clusters and calcium release units (CRUs) which control channel activity. These structures demonstrate nanoscale remodeling in disease states associated with pathological Ca2+ release activity in the heart. Hence, these nanoscale structures are critical in regulating Ca2+ release in health and disease. RyR2 is also expressed in brain; however, whether analogous clusters and CRUs form in neurons remains unexplored. Using super-resolution imaging, we assessed RyR2 organization in CA1 pyramidal neurons of wild-type mice. Furthermore, we used the APP/PS1 mouse model of Alzheimer's disease (AD) to assess whether there is nanoscale remodeling of RyR2 in a setting associated with pathological Ca2+ release in neurons. Here, we provide the first identification and detailed characterization of RyR2 clusters in central nervous system neurons, which are comparable to those reported in the heart. Moreover, we observed a decrease in RyR2 cluster size and reduced CRU organization in AD mice at an age associated with high plaque burden and cognitive deficits. This remodeling is analogous to that reported in pathological states in the heart. Together, these findings implicate the nanoscale remodeling of RyR2 clusters and CRUs as a novel mechanism underlying Ca2+ channel dysregulation and neuronal dysfunction in AD.
Architected metamaterials derive their exceptional mechanical performance from their precisely-tailored underlying topologies, enabling access to regions of materials selection charts unattainable by conventional materials. While substantial advances have been achieved at micro-, meso-, and macroscales, further improvements are increasingly constrained, motivating exploration of nanoscale architected materials where surface and size effects dominate the overall multiphysics performance. Here, we resort to molecular dynamics simulations to systematically explore the mechanical response of nickel-based nano-architected metamaterials. By varying topology, relative density, crystallinity, and grain size, we demonstrate the broad tunability of elastic moduli, strength, and Poisson's ratio enabled by the rational design of underlying nano-architecture. Notably, the proposed nano-architected metamaterials outperform most previously reported architected materials at comparable densities, highlighting the effectiveness of nanoscale topology-driven designs. Atomistic analyses reveal that nanoscale free surfaces promote dislocation nucleation while inhibiting dislocation propagation, leading to flow stresses exceeding those of bulk counterparts. To bridge length scales and draw inspiration from crystallography, we design and 3D print hierarchical polymeric metamaterials and experimentally characterize their mechanical behavior. Despite being fabricated from an intrinsically brittle polymer, these structures exhibit topology-dependent stiffness and strength, alongside ductile plastic deformation and enhanced toughness, attributable to their hierarchical architectures. Together, this work introduces a crystallography-inspired architectural design paradigm for mechanical metamaterials and imparts scalable guidelines for achieving lightweight, mechanically efficient structures across multiple length scales.
Three-dimensional metastructures with nanoscale feature sizes exhibit unique properties compared with structures with larger feature sizes, but are difficult to fabricate. Here we introduce implosion carving (ImpCarv), a method for photopatterning vacancies of complex geometry throughout materials, followed by isotropic shrinkage (>10-fold). ImpCarv works by photoactivating sensitizers to generate reactive oxygen species that cleave a swollen hydrogel at defined points, followed by controlled shrinkage via dehydration. ImpCarv creates three-dimensional metastructures where the refractive index of each point throughout a material can be specified with nanoscale precision via material presence or absence. By leveraging refractive index programmability for precise phase control, we demonstrate an all-optical machine learning device with nanoscale neuron sizes operating at visible wavelengths. ImpCarv may thus support diverse applications in nanophotonics and nanotechnology.
Plasmonic nanostructures enable light-driven chemical transformations through localized electromagnetic fields and hot-carrier generation. Here, we demonstrate that amide bond formation between carboxylic acids and amines, which is thermodynamically unfavorable under ambient conditions, can be directly driven in plasmonic nanogaps without coupling agents or thermal activation. Under resonant excitation, hot electrons generated in the nanogap activate the carbonyl group within a spatially confined environment, enabling a nucleophilic attack and subsequent bond formation. In situ surface-enhanced Raman spectroscopy reveals the emergence of amide vibrational modes, supported by density functional theory calculations. The reaction exhibits a clear excitation power threshold, is suppressed under off-resonant conditions, and is not induced by thermal heating alone, confirming its nonthermal origin. Furthermore, plasmon-induced nanoparticle aggregation provides independent evidence of covalent bond formation at the nanoscale. These findings establish plasmonic nanogaps as functional reaction environments that enable reactions without coupling agents and demonstrate that nanoscale confinement and localized electronic excitation can drive thermodynamically challenging transformations.
Morphology is a critical determinant of the photovoltaic performance of organic solar cells (OSCs), as it governs charge generation, separation, and transport by regulating nanoscale phase separation and molecular packing within the active layer. Among the various strategies developed to control morphology, solid additives (SAs) have emerged as a particularly promising approach. Offering advantages such as low cost and ease of incorporation, SAs enable precise tuning of active layer morphology without the need for complex synthetic modification. By promotion of favorable nanoscale phase separation, SAs can facilitate the formation of well-organized domains that enhance charge transport pathways while reducing charge recombination losses. Recent advances have underscored the significant potential of SA engineering in advancing OSCs toward large-scale commercial deployment. This review provides a comprehensive summary of recent progress in SA development with a particular emphasis on their roles in regulating film formation dynamics and optimizing morphologies. Finally, we highlight the remaining challenges and propose future research directions to further exploit SA engineering in the realization of high-efficiency, stable organic photovoltaic devices.
Terahertz (THz) radiation provides an effective means to probe and manipulate collective molecular dynamics in confined water. In this work, nonequilibrium molecular dynamics simulations are employed to investigate the frequency-dependent thermal response and microscopic structure of water confined in armchair-type double-walled carbon nanotubes (DWCNTs). Water encapsulated in (3, 3)@(13, 13), (3, 3)@(18, 18), and (3, 3)@(23, 23) DWCNTs is subjected to linearly polarized THz electric fields applied either parallel or perpendicular to the nanotube axis, and the resulting temperature jump, ΔT, is analyzed over a broad THz frequency range. In comparison with bulk water, confined water exhibits substantially enhanced and highly frequency-selective heating, with a pronounced dependence on field polarization. Under axial polarization, water confined in the narrowest (3, 3)@(13, 13) DWCNT shows a strong resonant response, yielding a maximum temperature increase of ΔT ∼ 370 K, approximately 3.3 times that of bulk water. This enhancement weakens systematically with increasing outer nanotube diameter and higher initial temperature. Analyses of oxygen-oxygen radial distribution functions and transverse density profiles reveal that nanoscale confinement induces pronounced molecular ordering and spatial localization, characterized by ring-like density distributions within the nanotube cross section. These confinement-induced structural features indicate a strong coupling between collective molecular motions and external THz fields, demonstrating that geometric confinement and field polarization jointly regulate resonant energy absorption in nanoscale aqueous systems.
The fast-charging capability has become a critical performance requirement for next-generation lithium-ion batteries (LIBs). Layered high-nickel transition metal oxides (LiNixCoyMn(1-x-y)O2, x ≥ 0.8) have emerged as the most promising candidates due to their high specific capacity and energy density toward fast-charging LIBs. However, their practical implementation under fast-charging conditions is severely hindered by sluggish Li+ diffusion kinetics and interfacial instability. While a high Ni content effectively boosts capacity, it inevitably compromises structural robustness and accelerates surface degradation. Conventional surface coating methods, which typically target secondary particles, often suffer from nonuniform coverage and incomplete interfacial protection. To overcome these bottlenecks, we propose a novel surface engineering strategy that electrochemically constructs a conformal fast-ion-conducting layer directly on the primary particles of Ni-rich cathodes. High-resolution transmission electron microscopy equiped with energy-dispersive X-ray spectroscopy combined with time-of-flight secondary ion mass spectrometry (ToF-SIMS) verify the conformal and homogeneous nanoscale Li2SeO4 coating on primary particles, while Galvanostatic Intermittent Titration technique and Density Functional Theory calculations collectively demonstrate its fast Li+-ion transport characteristics, featuring a migration barrier as low as 260 meV. This strategy significantly improves high-rate performance (180.6 mAh·g-1 at 10C) and cycling durability (94.2% capacity retention after 100 cycles). This work presents a versatile and scalable interfacial engineering approach for advancing fast-charging layered cathode materials.
Microelectrode arrays are an essential tool for interfacing with nerve tissue to better understand brain functioning, as well as for therapeutic applications. Yet, the structural customizability of microelectrode arrays and the integration of specific materials into electrode designs remain challenging. Two-photon polymerization (2PP) is a high-resolution additive fabrication technique capable of producing micro- and nanoscale architectures, thus offering design flexibility for microelectrode arrays. However, due to the limited electrical conductivity of photo-cross-linkable polymers, 2PP three-dimensional (3D) printing is not widely adopted for the fabrication of microelectrode arrays yet. In this work, we present the millimeter-scaled integration of the conductive polymer poly(3,4-ethylenedioxythiophene):tetrafluoroborate (PEDOT:BF4) into 2PP 3D-printed neural probe architectures via electrochemical deposition. Unlike state-of-the-art thin-film PEDOT coatings, this approach enables the formation of vertically extended, entirely polymer-based electrodes with a length in the millimeter range. These all-polymer electrode arrays exhibit low impedance, excellent electrochemical and mechanical stability, and enable neural recordings in freely moving rats. This fabrication process may thus provide a platform technology for customizable microelectrode arrays, demonstrating the effective integration of a conductive polymer into 2PP 3D-printed microneedle arrays. This platform could be leveraged for a wide range of applications in the broader field of bioelectronics.
Yam starch (YS) has inherently weak gel strength because of its high amylopectin content, which critically restricts its advanced applications in the food industry. This study investigated the effect of incorporating high-amylose mung bean starch (MBS) (0-4%) as a natural modifier on YS gel properties. Results showed that MBS addition dose-dependently enhanced pasting temperature, viscosity, viscoelastic moduli, hardness, chewiness, and thermal stability of YS gels. Microstructurally, it led to a denser gel network with a smoother, more homogeneous nanoscale surface. X-ray diffraction (XRD) and Fourier transform infrared (FTIR) spectroscopy analyses indicated that MBS suppressed long-range crystallinity of YS gels but promoted short-range order and formed more junction zones within the amorphous network, resulting in an amorphously reinforced gel matrix. This reinforcement was ascribed to the competitive hydrogen bonding and cross-linking between MBS amylose and YS components. The work provides a green strategy for designing starch-based gels with tunable texture and improved stability for food applications.
The deformation and rupture of a lipid vesicle due to the forced normal approach of an inclusion are essential for optimizing the design of magnetic giant unilamellar vesicles (GUV) [Malik et al., Nanoscale 17, 13720 (2025)NANOHL2040-336410.1039/D5NR00942A], with implications for active colloid-membrane interactions and cellular-scale chemical delivery. Here, we investigate vesicles propelled by a force-driven rigid inclusion and reveal a robust elastohydrodynamic mechanism: the inclusion outpaces the vesicle, sustaining a thinning film that drains symmetrically and self-similarly, largely independent of the initial shape. For soft membranes and small inclusions, the coupling drives a monotonic tension increase that can exceed the lysis tension. Evaluating the maximal tension over a delivery distance, we map an operating window in a vesicle reduced area and size relative to the inclusion.
Transcription of eukaryotic genes by RNA Polymerase II occurs in temporal bursts and spatial clusters. It is regulated by dozens of transcription factor and coactivator proteins and guided by epigenetic histone marks. Colocalization of transcription machinery in dense foci suggests that cooperative effects orchestrate the process. Factory or condensate models provide a framework for the spatial assembly of the transcription machinery at highly active chromatin loci. But conventional methods lack the resolution to determine how chromatin regulatory elements interact with spatial clusters of the transcription machinery, and whether chromatin structural features modulate functional output. Here, we use super-resolution microscopy to elucidate nanoscale organization of regulatory chromatin at Pol II clusters across scales. We find that Pol II clusters exist on a continuous spectrum of sizes and represent promoter chromatin hubs. We uncover a layered organization of regulatory chromatin, where Pol II clusters form at H3K27ac and H3K4me3-rich domains while H3K4me1 positions peripherally at the surface of large Pol II clusters. Perturbation experiments are consistent with a model in which cohesin loop extrusion forms the active chromatin scaffold underlying transcription assemblies while condensate-driven interactions play only a minor role in genome organization at these sites. Importantly, the number and size of transcriptional burst size increases with Pol II cluster size, revealing directly the cooperative benefits of transcription organization in promoter hubs and a functional consequence of local chromatin structure.
Breast cancer remains one of the leading causes of cancer-related mortality among women worldwide. Although methyltestosterone (MT) has demonstrated therapeutic potential in hormone-responsive breast cancer, its clinical application may be limited by poor aqueous solubility and non-specific distribution. Albumin-based nanocarriers may enhance drug stability and intracellular availability. This study aimed to develop genipin-crosslinked human serum albumin (HSA) nanoparticles loaded with MT and to evaluate their physicochemical properties, release behavior, and in-vitro pharmacological and cytotoxic effects in MCF-7 breast cancer cells. MT-loaded HSA nanoparticles were prepared using the desolvation method followed by genipin crosslinking. Particle size, polydispersity index (PDI), and zeta potential were determined by dynamic light scattering (DLS), while morphology and crystallinity were evaluated using SEM and XRD analysis. Drug loading (DL) and encapsulation efficiency (EE) were quantified spectrophotometrically. In-vitro release was assessed under different pH conditions (5.5, 6.8, and 7.4). Cytotoxicity and pharmacological activity were evaluated in MCF-7 cells using MTT, LDH, and TUNEL assays. Statistical analysis was performed using one-way ANOVA (p < 0.05). The formulated MT-HSA nanoparticles exhibited a mean diameter of 83 nm (PDI 0.25) and a zeta potential of - 16.3 mV, indicating uniform nanoscale distribution and moderate colloidal stability. Encapsulation efficiency and drug loading were 77% and 11%, respectively. Sustained and pH-dependent drug release was observed over 100 h, with higher release under acidic conditions (83% at pH 5.5). MT-HSA nanoparticles significantly reduced MCF-7 cell viability compared with free MT (p < 0.05), accompanied by increased LDH release and higher apoptotic index in TUNEL assays. Unloaded HSA nanoparticles showed negligible cytotoxicity. The formulation remained physically stable for two months at 4 °C. Genipin-crosslinked MT-HSA nanoparticles demonstrated improved in-vitro pharmacological efficacy, enhanced cytotoxic and pro-apoptotic activity compared with free methyltestosterone, and favorable carrier biocompatibility. These findings support albumin-based nanoencapsulation as a promising strategy for optimizing steroid-based therapy in hormone-responsive breast cancer, although further in-vivo studies are required to confirm translational potential.
Liquid-phase transmission electron microscopy (LPTEM) enables real-time visualization of nanoscale dynamics in electrochemical, biological, and catalytic reactions. However, accelerated electrons employed as probes can perturb the chemical environment through electron-liquid interactions, thereby complicating reliable data acquisition and interpretation. Although these interactions have been studied based on kinetic modeling of water radiolysis, a comprehensive understanding of the influence of interfaces and confinement within microfluidic liquid cells remains less understood. Prior γ-irradiation and electron-beam studies have shown that adsorbed water on solid-liquid interfaces can dramatically modify radical yields, yet the effect of specific interfaces in liquid cells on radiolysis has been less understood. Herein, we reveal effects at interfaces and their influence on water radiolysis by liquid-cell interface engineering using radiolysis-driven oxidative etching of palladium nanocubes as a probing system. Complementary density functional theory calculations show that graphene coatings suppress interfacial water dissociation and electron transfer, thereby modulating beam interaction pathways.