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.
Magnetic nanoparticle heating (MNH) enables nanoscale energy delivery, yet current predictions of nonequilibrium magnetic dynamics at the single-particle level often lack quantitative experimental validation across nanoparticle regimes and field conditions. Here, we combine experimentally derived composite magnetic anisotropy with a stochastic Landau-Lifshitz-Gilbert description to quantitatively model MNH across superparamagnetic and magnetically blocked ferrimagnetic regimes. Simulations reproduce macroscale calorimetric heating measurements across broad particle sizes and field conditions while revealing how cycle-resolved stochastic magnetic switching contributes to heat generation. This approach shows how stochastic thermal fluctuations and anisotropy-governed dynamics give rise to classical hysteresis behavior at the macroscale, providing a multiscale physical framework for modeling energy dissipation in complex magnetic nanomaterials.
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.
Real-time, in situ monitoring of neurochemical dynamics in intact neural circuits is critical for elucidating brain function. Recent innovations in micro- and nanoelectrode engineering have markedly advanced our ability to detect neurotransmitter and neuromodulator release with high spatiotemporal resolution, while the application of machine learning (ML) has facilitated the development of next-generation electrodes and enhanced signal processing capabilities. Here, we outline a vision for the potential directions for electrode interface design and the deepening integration of ML in in situ neurochemical sensing, illustrating how breakthroughs over the past decade have illuminated these opportunities.
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.
The multi-scale organization of chromatin underlies gene regulation and cell identity, yet how nuclear architecture remodels during cell state transitions remains poorly understood. Here, we use single-molecule localization microscopy and a comprehensive analytical framework we call O-SNAP to reveal distinct chromatin remodeling trajectories in two biological contexts: dedifferentiation in chondrocytes and nuclear oxidative stress-induced remodeling in mammary epithelial cells. Conventional analyses of single-molecule localization microscopy chromatin images based on qualitative inspection or simple metrics, such as chromatin domain size, fail to capture the subtle chromatin transitions in both contexts. In contrast, O-SNAP quantitatively integrates and compares 144 spatial features extracted from single-molecule localization microscopy data, allowing machine-learning based classification of nuclear states and systematic downstream analyses such as feature selection, volcano plots, and feature set enrichment analysis to determine which spatial features most strongly drive classification results. Our analysis shows that in chondrocytes, in vitro passaging drives heterochromatin formation at late passages, whereas intermediate passages exhibit heterogeneous chromatin remodeling. In contrast, in mammary epithelial cells, nuclear oxidative stress leads to chromatin decompaction specifically in cells overexpressing the oxidation-sensitive histone H3.1 variant. Together, these findings demonstrate that integrated, multiscale spatial features of chromatin are sufficient to robustly discriminate distinct cellular states.
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.
Atomically thin nanotubes of semiconducting transition metal dichalcogenides offer a platform for exploring quantum phenomena at the one-dimensional limit and for realizing nanoscale transistor channels. However, conventional syntheses produce only large-diameter (>10 nm), multiwalled tubes with uncontrolled chiralities. We report the synthesis of single-walled molybdenum disulfide (MoS2) nanotubes with diameters approaching 1 nm, achieved through spatially confined reactions inside boron nitride (BN) nanotubes. The confined geometry stabilizes otherwise inaccessible, highly strained MoS2 nanotubes, yielding structurally well-defined armchair configurations. Their bandgaps shrink systematically with decreasing diameter, in accordance with long-standing theoretical predictions. The insulating BN sheath simultaneously provides an intrinsic gate-all-around architecture, thereby promising access to truly nanoscale transistor channels.
The ability to encode and reliably read nanoscale information is increasingly important for multiplexed biomolecular detection and super-resolution imaging. DNA origami provides a uniquely programmable platform for arranging structural and functional elements with nanometer precision, enabling the creation of identifiable nanoscale patterns. In this context, DNA origami-based barcodes that incorporate gold nanoparticles (AuNPs) to encode either origami geometry or the identity of specific biological targets within defined nanoparticle patterns have been paired with transmission electron microscopy imaging for decoding. However, surface-bond AuNPs may detach during handling, purification, or biological incubation, leading to misidentification or decoding errors in barcode analysis. Here we report a rational design for the controlled encapsulation of AuNPs within DNA origami tubes to enhance nanoparticle retention and structural integrity. We engineered curvature-inducing modifications in a flat rectangular DNA origami scaffold to promote inward folding and confinement of AuNPs. These barcodes can be further functionalized on the outer surface with bioactive aptamers and/or fluorescence dyes, enabling targeted interactions with cells and optical readout. Programable dimerization further expands multiplexing capacity. This design provides a robust framework for structurally stable origami barcodes and advances the development of high-resolution, multiplexed labeling and diagnostic platforms.
Natural polymers represent promising materials for sustainable applications such as food packaging. However, their use remains limited due to poor mechanical performance, high water sensitivity, and insufficient barrier properties. Multilayer structures can overcome these drawbacks by integrating complementary materials, for which interfacial compatibility is critical. Herein, colloidal-probe atomic force microscopy (AFM) was used to quantify nanoscale adhesion forces and elucidate interfacial interactions in biopolymer-based multilayer films. The films were constructed from polysaccharides, specifically carboxymethylcellulose (CMC), and proteins, casein and zein, assembled with and without tannic acid (TA) as a cross-linker. AFM adhesion measurements obtained using a casein-modified probe were correlated with macroscale delamination, surface wettability, water vapor permeability, and water uptake. Casein-CMC interfaces exhibited a low normalized pull-off force (0.005 mN·m-1), which increased to 0.02 and 0.04 mN·m-1 upon incorporating 5% and 30% of TA, respectively. Enhanced adhesion with longer probe-substrate contact time supported interfacial cross-linking between CMC and proteins mediated by TA. This cross-linking also improved moisture resistance, evidenced by an 80% reduction in equilibrium moisture content in TA-containing casein-CMC bilayer films. The adhesion between casein and zein (both in terms of normalized pull-off forces and normalized adhesion energies) was significantly higher than between casein and CMC, indicating strong protein-protein affinity. However, this protein-protein adhesion was insensitive to TA, likely due to intralayer cross-linking as opposed to interlayer cross-linking. Colloidal-probe AFM was an effective approach for resolving interfacial interactions to expand the versatility of biopolymer-based multilayer packaging, and for highlighting the role of nanoscale adhesion in guiding materials selection and interface engineering.
ConspectusNitrogen-vacancy (NV) centers in diamond are a unique class of quantum defects distinguished by their exceptional optical and magnetic properties, including bright photoluminescence, outstanding photostability, and optically addressable spin states. In nanoscale diamonds, commonly referred to as fluorescent nanodiamonds (FNDs), NV centers can exist in both neutral (NV0) and negatively charged (NV-) states. These nanoparticles are chemically inert, highly biocompatible, and readily amenable to surface functionalization. Together, these attributes have established FNDs as powerful biological quantum probes since their introduction in 2005. Notably, the same optical and spin properties that enable their success in biological environments also underpin their utility in more demanding physical and engineering contexts. This Account highlights three emerging applications that arise from this shared foundation: immunodiagnostics, extreme ultraviolet (EUV) metrology, and semiconductor device analysis.First, we show that FNDs with NV- centers are excellent fluorescent quantum reporters for quantitative immunoassays employing antibodies for specific antigen detection. A key limitation of traditional fluorescence-based immunoassays is the high background from substrates like nitrocellulose membranes, which significantly reduces detection sensitivity. This challenge is overcome by combining laser excitation with lock-in detection of magnetically modulated fluorescence from NV- centers in FNDs to effectively eliminate background interference. The approach has enabled highly sensitive, high-throughput, quantitative, and rapid biomarker detection, marking a practically useful application of NV quantum defects in healthcare diagnostics.Second, FNDs with NV0 centers have emerged as a novel type of scintillator for EUV sensing and imaging. These carbon-based scintillators are fabricated into uniform, thin, and chemically stable films using electrospray deposition. They emit bright red fluorescence from NV0 centers when FNDs are exposed to EUV radiation at wavelengths of 13.5 nm. The scintillators are nonhygroscopic, photostable, and compatible with fiber-optic plates and sensors, allowing for integration into compact, high-resolution detection systems. These properties render them highly suitable for real-time, long-term imaging in the EUV and soft X-ray regimes, particularly for photolithographic applications.Third, FNDs with NV- centers are quantum sensors capable of measuring temperature, magnetic, and electric fields at the nanoscale. These measurements are crucial for the design and evaluation of next-generation semiconductor devices. An innovative technique, termed FND-based lock-in photoluminescence thermography, has been developed to enable wide-field, real-time temperature mapping of actively operating devices such as bipolar junction transistors and field-effect transistors. The method achieves nanometer-scale spatial resolution and millisecond temporal resolution, yielding valuable insights into heat generation and dissipation processes in operando semiconductor devices.In summary, NV centers in FNDs constitute robust platforms for quantum sensing and metrology across a broad range of domains. From enhancing the sensitivity of immunodiagnostics to advancing EUV imaging and improving semiconductor thermal analysis, these quantum defects serve as transformative tools at the intersection of materials chemistry, biomedicine, and quantum technologies.
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.
Enamel covers teeth, is the hardest tissue in the vertebrate body and has a complex multiscale structure from nanometres to millimetres1. The structure comprises thin, long hydroxyapatite (Ca5(PO4)3OH) nanocrystals2, 50-70 nm wide, many micrometres long, parallel and bundled into approximately 5-µm-wide rods. The rods undulate and cross into a microscale 'decussation pattern' that toughens enamel by deflecting cracks3,4. However, the crystallographic orientation of enamel nanocrystals is poorly understood. Here we show that the misorientation angle of adjacent nanocrystals varies markedly across 12 primate teeth spanning 9 species, 17.8 million years of evolution and diverse diets. Using a method called Polarization Enabled Large Input of Crystal Angles at the Nanoscale (PELICAN)5, we compare nanocrystals in the same (pre)molar locations and show that misorientation increases with food hardness in extant and fossil non-human apes and monkeys. We compare misorientation across three major dietary shifts in human evolution: the transition to meat-eating about 2.0-1.5 million years before present6,7, to agriculture (about 12,000 years before present)8,9, and the Industrial Revolution (about 250 years before present)10. We show that over the past 1.6 million years, in the human lineage misorientation increased with time, especially when meat and stone-ground grains were introduced into human diets, but not with the Industrial Revolution. Thus, besides macro-changes, teeth adapted to dietary change at the nanoscale and crystallographically. This observation suggests that misorientation may contribute to enamel's resilience; thus, bioinspired materials may consider small misorientation angles for added resilience.
Recent advances in instrumentation have sparked a transformative journey in materials science, providing insights into the intricate relationship between processing, structure and properties. Among them, cutting-edge in situ micro- and nanoscale mechanical characterization methods, equipped with exceptional spatial and temporal resolution, such as instrumented electron microscopy, X-ray imaging and opto-acoustic techniques, have opened new frontiers in the study of emerging functional and architected materials, including low-dimensional materials, bio-inspired materials and three-dimensional architected metamaterials, underscoring the versatility of these innovative characterization techniques. Furthermore, the integration of artificial intelligence and machine learning offers promising opportunities to streamline high-throughput experimentation processes and enhance the efficiency and accuracy of characterization, and promote the design of next-generation materials. This Review provides a comprehensive overview of the latest micro- and nanoscale mechanical characterization methods. We highlight their interdisciplinary applications to functional and architected materials in the pursuit of solutions for energy, sustainability, semiconductor technology and healthcare.
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.
Surface-enhanced Raman spectroscopy (SERS) offers exceptional sensitivity but faces a critical trade-off in living systems: rigid substrates lack biological adaptability, while colloidal nanoprobes suffer from poor signal reproducibility. Herein, we present a bioadaptive SERS platform using magnetically guided swarming nanoprobes. These probes integrate a magnetic core, plasmonic gold/silver layers, and a biocompatible silica coating, enabling programmable assembly under magnetic fields into chain-like nanostructures with interparticle gap-dependent hotspots, followed by coordinated reconfiguration into dynamically stable swarms. Multiphysics simulations reveal that cyclic assembly-disassembly generates transient electromagnetic hotspots while inducing convective flows to actively recruit analytes. This dual mechanism achieves reproducible enhancement factors exceeding 2.9×107, an order of magnitude higher than colloidal systems. In vivo, swarming nanoprobes deployed in rabbit models demonstrate over 10.3-fold Raman signal amplification during intravascular detection. By leveraging active matter physics to synergize nanoscale sensing, this work establishes a new paradigm for in vivo molecular diagnostics.
Fellhauer et al. report the first plutonyl cage cluster, {Pu60}, marking a major advance in plutonium chemistry (DOI:10.1002/anov.70018). Its unique distorted truncated dodecahedral topology expands the known library of aqueous actinide species and points toward nanoscale control of plutonium through tunable cage structures, counter-cations, and ligand substitutions.
This work developed and evaluated a crocin-coated zinc-sodium alginate-polyethylene glycol (Zn/SAG/PEG/Cr) nanocomposite as a potential therapeutic against bladder cancer using T24 human carcinoma and Vero kidney epithelial cells. Systematic characterization confirmed successful zinc incorporation, a crystalline inorganic phase, and nanoscale particle size with high compositional purity. MTT assay demonstrated that the nanocomposite exerts selective, concentration-dependent cytotoxicity against T24 cells while maintaining biocompatibility with normal Vero cells. Mechanistic analysis revealed that treatment of the nanocomposite significantly enhanced intracellular reactive oxygen species (ROS) generation, disrupted mitochondrial membrane potential, and compromised plasma membrane integrity. Furthermore, the nanocomposite suppressed pro-inflammatory mediators (TNF-α, NF-κB, COX-2, and IL-6) and induced apoptosis, evidenced by elevated Bax, caspase-3, and caspase-9 levels alongside reduced Bcl-2 expression. Crucially, the formulated nanocomposite attenuated the PI3K/Akt/mTOR signaling pathway, a key regulator of bladder cancer progression. Despite these potent anti-oncogenic effects, challenges remain regarding the precise control of crocin release kinetics and the long-term metabolic clearance of the metallic zinc component. Future prospects involve validating these findings in orthotopic animal models to assess systemic toxicity and optimizing the formulation for targeted intravesical delivery to improve clinical translation.