Reversible Interactions Research Articles

A chemical genetic screen with the EXO70 inhibitor Endosidin2 uncovers potential modulators of exocytosis in Arabidopsis.

Exocytosis plays an essential role in delivering proteins, lipids, and cell wall polysaccharides to the plasma membrane and extracellular spaces. Accurate secretion through exocytosis is key to normal plant development as well as responses to biotic and abiotic stresses. During exocytosis, an octameric protein complex named the exocyst facilitates the tethering of secretory vesicles to the plasma membrane. Despite some understanding of molecular and cellular aspects of exocyst function obtained through reverse genetics and direct interaction assays, knowledge about upstream modulators and genetic interactors remains limited. Traditional genetic screens encounter practical issues in exocyst subunit mutant backgrounds, such as lethality of certain knockout mutants and/or potential redundancy of EXO70 homologs. To address these challenges, this study leverages the tunable and reversible nature of chemical genetics, employing Endosidin2 (ES2)-a synthetic inhibitor of EXO70-for a large-scale chemical genetic mutant screen in Arabidopsis. This approach led to the identification of 70 ES2-hypersensitive mutants, named es2s. Through a whole-genome sequencing-based mapping strategy, 14 nonallelic es2s mutants were mapped and the candidate mutations reported here. In addition, T-DNA insertion lines were tested as alternative alleles to identify causal mutations. We found that T-DNA insertion alleles for DCP5, VAS1/ISS1, ArgJ, and MEF11 were hypersensitive to ES2 for root growth inhibition. This research not only offers new genetic resources for systematically identifying molecular players interacting with the exocyst in Arabidopsis but also enhances understanding of the regulation of exocytosis.

The Development of Non-natural Type Nucleoside to Stabilize Triplex DNA Formation against CG and TA Inversion Site.

Based on the sequence-specific recognition of target duplex DNA by triplexforming oligonucleotides (TFOs) at the major groove side, the antigene strategy has been exploited as a gene-targeting tool with considerable attention. Triplex DNA is formed via the specific base triplets by the Hoogsteen or reverse Hoogsteen hydrogen bond interaction between TFOs and the homo-purine strand from the target duplex DNA, leading to the established sequence-specificity. However, the presence of inversion sites, which are known as non-natural nucleosides that can form satisfactory interactions with 2'- deoxythymidine (dT) and 2'-deoxycytidine (dC) in TA and CG base pairs in the target homo-purine DNA sequences, drastically restricts the formation of classically stable base triplets and even the triplex DNA. Therefore, the design of non-natural type nucleosides, which can effectively recognize CG or/and TA inversion sites with satisfactory selectivity, should be of great significance to expanding the triplex-forming sequence. Here, this review mainly provides a comprehensive review of the current development of novel nonnatural nucleosides to recognize CG or/and TA inversion sites in triplex DNA formation against double-strand DNA (dsDNA).

Surface-Roughened Graphene Oxide Microfibers Enhance Electrochemical Reversibility.

Here, we provide an optimized method for fabricating surface-roughened graphene oxide disk microelectrodes (GFMEs) with enhanced defect density to generate a more suitable electrode surface for dopamine detection with fast-scan cyclic voltammetry (FSCV). FSCV detection, which is often influenced by adsorption-based surface interactions, is commonly impacted by the chemical and geometric structure of the electrode's surface, and graphene oxide is a tunable carbon-based nanomaterial capable of enhancing these two key characteristics. Synthesized GFMEs possess exquisite electronic and mechanical properties. We have optimized an applied inert argon (Ar) plasma treatment to increase defect density, with minimal changes in chemical functionality, for enhanced surface crevices to momentarily trap dopamine during detection. Optimal Ar plasma treatment (100 sccm, 60 s, 100 W) generates crevice depths of 33.4 ± 2.3 nm with high edge plane character enhancing dopamine interfacial interactions. Increases in GFME surface roughness improve electron transfer rates and limit diffusional rates out of the crevices to create nearly reversible dopamine electrochemical redox interactions. The utility of surface-roughened disk GFMEs provides comparable detection sensitivities to traditional cylindrical carbon fiber microelectrodes while improving temporal resolution ten-fold with amplified oxidation current due to dopamine cyclization. Overall, surface-roughened GFMEs enable improved adsorption interactions, momentary trapping, and current amplification, expanding the utility of GO microelectrodes for FSCV detection.

Cellulose nanocomposite tough hydrogels: synergistic self‐healing, adhesive and strain‐sensitive properties

AbstractRecent advancements are notable in electrically conductive hydrogels emulating human skin functions. However, a significant challenge remains: crafting a single conductive gel that integrates self‐healing, robust mechanical strength, and excellent electrical traits. Our innovation lies in a strong, lightweight, curable gel achieved through multiple coordination bonds between cellulose crystals and acid‐treated multi‐walled carbon nanotubes (MWCNTs) in a polymer network. Embedded MWCNTs act as dynamic bridges within a porous structure, giving exceptional mechanical performance. Reversible coordination interactions confer remarkable recovery and reliable mechanical and electrical self‐healing. Additionally, these ionic gels function as adaptable stress sensors, detecting significant movements like finger and joint motions. This work introduces MWCNT‐incorporated nanomaterials with good stretchability, high ion conductivity, remarkable self‐healing nature, and good stress sensitivity. Such proteins hold promise for electronic sensors, wearable devices, and healthcare monitoring, unveiling a path to diverse applications. Our study addresses challenges and unlocks possibilities for materials that can adapt, withstand, and sense in innovative ways. © 2024 Society of Chemical Industry.

Fiction meets fact: exploring human-machine convergence in today’s cinematographic culture

Abstract This article explores the theme of human-machine convergence as portrayed in modern science fiction movies and TV/streaming series and compares them to real-world advancements in robotics, artificial intelligence (AI), and virtual reality (VR). It examines how science fiction often depicts humanoid robots and AI with human-like emotions and intentions, contrasting with the actual technological challenges and ethical considerations in developing intelligent machines. The text discusses the evolution of humanoid robots from fictional portrayals to real-life examples like Boston Dynamics’ Atlas and Tesla’s Optimus. The paper also explores the reverse interaction, where humans become avatars in virtual worlds, and briefly discusses the ethical implications of simulating deceased individuals in digital form. Through this examination, the paper emphasizes the complexity of human-machine convergence and the importance of considering social, ethical, and emotional aspects in technological progress. It concludes by suggesting that while science fiction provides insights into societal fears and hopes regarding technology and thus into ethical and regulative necessities, the real trajectory of human-machine convergence cannot be predicted through film but will be determined by ongoing and after all incidental developments in the real world.

Self-healing glassy hybrids based on imidazole-functionalized silica nanoparticles with zinc complexes using dynamic and reversible cross-linking

Self-healing glass materials can potentially overcome the inherent limitations of glass, such as brittleness and difficulties in repairing broken sections while maintaining its critical properties. This paper reports a structural design and synthetic strategy for preparing glassy self-healing hybrids with high silica contents. The developed hybrids exhibited excellent self-healing properties based on dynamic and reversible crosslinking owing to the high density of zinc/imidazole units on the silica surface. First, core–shell silica nanoparticles with small multifunctional imidazole/butyl units (diameter: approximately10 nm) and good processability (homogeneous colloidal dispersions in common organic solvents) were synthesized. Afterwards, imidazole-functionalized silica nanoparticles were fabricated using Zn species to obtain self-healing hybrids with high silica contents (>60 wt%). These nanoparticles served as multifunctional and reversible crosslinking sites that dissipated energy, resulting in excellent mechanical, thermal, and healing characteristics. The obtained zinc/imidazole-based silica hybrids remain solid with high storage elasticity in the temperature range of 25–160 °C and high thermal stability corresponding to a 5 wt% weight loss above 280 °C, which were critical for self-healing glass applications. They also exhibited a moderate Young’s modulus of 330 MPa and a self-healing recovery efficiency of 87%. The findings of this study provide new insights into the roles of reversible interactions (metal/ligand exchange reactions) at particle–particle interfaces and high surface functionalities that serve as non-covalent crosslinking points. The prepared hybrids with high silica contents remain solid over a wide temperature range, which can open new avenues for self-healing glass materials.

Stretchable Tb-Tb Distance Regulates the Piezofluorochromic Behavior of Chiral Tb(III)-MOF upon Compression.

Luminescent chiral Tb-MOF microcrystals with the Tb2(COO)4 subunit indicated strong green mechano-luminescence under compression. Furthermore, piezofluorochromic behavior in the diamond anvil cell was observed, with the intensity tendency of decreasing-increasing-decreasing and a shortened lifetime upon compression, due to the reversible stretchable Tb-Tb interactions. The Tb-Tb distance upon compression was refined through in situ high-pressure X-ray absorption spectra, which was consistent with the tendency of the piezofluorochromic intensity. In situ high-pressure UV-vis absorption spectra, Fourier transform infrared spectra, and powder X-ray diffraction demonstrated the full recovery of Tb-MOF after over 10 GPa compressions due to the semiflexible ligand. This work not only provided an ultrastable Tb-MOF but also illustrated the relationship of the piezofluorochromic behavior with the detailed structural transformation for the first time.

Self-Healing Polyurethane Elastomers with Superior Tensile Strength and Elastic Recovery Based on Dynamic Oxime-Carbamate and Hydrogen Bond Interactions.

The preparation of self-healing polyurethane elastomers (PUEs) incorporating dynamic bonds is of considerable practical significance. However, developing a PUE with outstanding mechanical properties and high self-healing efficiency poses a significant challenge. Herein, this work has successfully developed a series of self-healing PUEs with various outstanding properties through rational molecular design. These PUEs incorporate m-xylylene diisocyanate and reversible dimethylglyoxime as hard segment, along with polytetramethylene ether glycol as soft segment. A significant amount of dynamic oxime-carbamate and hydrogen bonds are formed in hard segment. The microphase separated structure of the PUEs enables them to be colorless with a transparency of >90%. Owing to the chemical composition and multiple dynamic interactions, the PUEs are endowed with ultra-high tensile strength of 34.5MPa, satisfactory toughness of 53.9MJ m-3, and great elastic recovery both at low and high strains. The movement of polymer molecular chains and the dynamic reversible interactions render a self-healing efficiency of 101% at 70°C. In addition, this self-healing polyurethane could still maintain high mechanical properties after recycling. This study provides a design strategy for the preparation of a comprehensive polyurethane with superior overall performance, which holds wide application prospects in the fields of flexible displays and solar cells.

Enhanced interaction of CO2 with TCNQ-modified CuO nanoparticle-infused PEO matrix: A novel approach in gas transport technology

We developed a composite membrane based on polyethylene oxide (PEO), achieving high CO2 selectivity, by incorporating 7,7,8,8-tetracyanoquinodimethane (TCNQ)-modified CuO nanoparticles into the PEO matrix. The addition of TCNQ helps in evenly distributing the CuO nanoparticles throughout the membrane, preventing them from clumping together. This treatment not only enhances the dispersion of CuO particles but also imparts a positive charge to their surface, which is beneficial for increasing the selectivity for CO2 over N2. The extent of this surface charge modification on the CuO nanoparticles was evaluated using X-ray photoelectron spectroscopy (XPS), while the synergy between the polymer and the additives was verified through Fourier-transform infrared (FT-IR) spectroscopy studies. The combination of CuO nanoparticles in the membrane contributes to both barrier and carrier effects, enhancing the gas selectivity. This is further aided by the intrinsic properties of PEO, a rubber-like polymer known for its good gas permeance. As a result of these combined effects, the PEO/CuO/TCNQ membrane exhibited a remarkable CO2 selectivity of 393 and a CO2 permeance of 3.9 gas permeation unit (GPU). The superior separation performance of this membrane can be ascribed to three main factors: enhanced solubility due to the oxide layer on the particle surfaces and in the polymer matrix, improved transport efficiency via reversible interactions thanks to the positively charged surface, and the effective barrier provided by the nanoparticles against N2 transport. These findings are expected to contribute significantly to future studies on the surface modification of metal nanoparticles and in the field of gas separation membranes.

Direct-ink-write 3D printing of highly-stretchable polyaniline gel with hierarchical conducting network for customized wearable strain sensors

The development of direct-ink-write (DIW) 3D printing conducting polymer gels with remarkable mechanical properties, satisfactory conductivity, and customized three-dimensional structures is in high demand for next-generation wearable strain sensors, yet challenging due to the difficulty of preparing conducting polymer solutions with high concentrations. Herein, a novel cellulose nanocrystal (CNC)-regulated polyaniline (PANI) composite ink for DIW 3D printing customized wearable strain sensors with high stretchability and hierarchical conducting networks is fabricated. With the employment of CNC as a stabilizer to regulate the intermolecular interactions, the in-situ polymerized composite ink achieves well-dispersed PANI and abundant reversible intermolecular interactions, which is favorable for DIW 3D printing PANI composite gel with tailored planar patterns of high geometric accuracy. Benefiting from the hierarchical gel frameworks and abundant non-covalent interactions within the PANI-based composite ink, the PANI composite gel exhibits remarkable stretchability, promising low-temperature tolerance and excellent strain sensing performance. Due to its unique wavy mesh structure, the DIW-printed PANI composite gel-based wearable strain sensor is more sensitive and can accurately detect changes in the human body. This work aims to expedite the advancement of DIW printing conducting polymer gel for the development of personalized wearable strain sensors and advanced flexible electronics.

Latest Evolution of the X-Ray Remnant of SN 1987A: Beyond the Inner Ring

Based on our Chandra imaging-spectroscopic observations, we present the latest evolution of the X-ray remnant of SN 1987A. Recent changes in the electron temperatures and volume emission measures suggest that the blast wave in SN 1987A is moving out of the dense inner ring structure, also called the equatorial ring (ER). The 0.5–2.0 keV X-ray light curve shows a linearly declining trend (by ∼4.5% yr−1) between 2016 and 2020 as the blast wave heats the hitherto unknown circumstellar medium (CSM) outside the ER. While the peak X-ray emission in the latest 0.3–8.0 keV image is still within the ER, the radial expansion rate in the 3.0–8.0 keV images suggests an increasing contribution of the X-ray emission from less dense CSM since 2012, at least partly from beyond the ER. It is remarkable that, since 2020, the declining soft X-ray flux has stabilized around ∼7 × 10−12 erg s−1 cm−2, which may signal a contribution from the reverse-shocked outer layers of ejecta as predicted by the three-dimensional magnetohydrodynamic models. In the latest ACIS spectrum of supernova remnant 1987A in 2022 we report a significant detection of the Fe K line at ∼6.7 keV, which may be due to changing thermal conditions of the X-ray emitting CSM and/or the onset of reverse shock interactions with the Fe ejecta.

A self-healing sustainable halloysite nanocomposite polyurethane coating with ultrastrong mechanical properties based on reversible intermolecular interactions

Endowing sustainable polyurethane (PU) materials with ultrastrong mechanical properties and highly efficient self-healing performancesimultaneously is extremely challenging and of great significance to dramatically extend the service life of metal materials. In this work, 4,4′-dithiodianiline (DTDA) and bio-based 2,5-Tetrahydrofurandimethanol (THFDM) were used as chain extenders to introduce hierarchical hydrogen bonds and aromatic disulfide bonds into the PU matrix, after which rich interfacial hydrogen bonds were obtained by incorporating environment-friendly polydopamine-modified halloysite nanotube (PDA@HNT) into the PU matrix. The developing PU nanocomposite exhibits record toughness (774.4 MJ m−3), outstanding tensile strength (68.3 MPa), and exceptional elongation at break (2882.7 %), as well as distinguished self-healing performance (85.4 % at 35 °C for 24 h; 95.9 % at 80 °C for 15 min). Thanks to the shielding effect of PDA@HNT fillers, the PU nanocomposite also possesses good corrosion resistance proved by its high impedance value at 0.01 Hz of 2.23 × 108 Ω cm2 after immersing in 3.5 wt% NaCl solution for 30 days. This work provides constructive guidance to create an ultra-robust self-healing sustainable PU nanocomposite with long-term corrosion resistance.

Robustly and Intrinsically Stretchable Ionic Gel-Based Moisture-Enabled Power Generator with High Human Body Conformality.

Direct harvesting of energy from moist air will be a promising route to supply electricity for booming wearable and distributed electronics, with the recent rapid development of the moisture-enabled electricity generator (MEG). However, the easy spatial distortion of rigid MEG materials under severe deformation extremely inconveniences the human body with intense physical activity, seriously hindering the desirable applications. Here, an intrinsically stretchable moisture-enabled electricity generator (s-MEG) is developed based on a well-fabricated stretchable functional ionic gel (SIG) with a flexible double-network structure and reversible cross-linking interactions, demonstrating stable electricity output performance even when stretched up to 150% strain and high human body conformality. This SIG exhibits ultrahigh tensile strain (∼600%), and a 1 cm × 1 cm SIG film-based s-MEG can generate a voltage of ∼0.4 V and a current of ∼5.7 μA when absorbing water from humidity air. Based on the strong adhesion and the excellent interface combination of SIG and rough fabric electrodes induced by the fabrication process, s-MEG is able to realize bending or twisting deformation and shows outstanding electricity output stability with ∼90% performance retention after 5000 cycles of bending tests. By connecting s-MEG units in series or parallel, an integrated device of "moisture-powered wristband" is developed to wear on the wrist of humans and drive a flexible sensor for tracking finger motions. Additionally, a comfortable "moisture-powered sheath" based on s-MEGs is created, which can be worn like clothing on human arms to generate energy while walking and flexing the elbow, which is promising in the field of wearable electronics.

Biomimetic dually cross-linked injectable poly(l-glutamic acid) based nanofiber composite hydrogels with self-healing, osteogenic and angiogenic properties for bone regeneration

Biomimetic hydrogels with satisfactory mechanical properties and osteogenic/angiogenic abilities have attracted extensive attention in recent years. Injectable hydrogels with the advantages of minimally invasive implantation and adaptability to irregular defects exhibit superior application potential in the field of bone regeneration. However, poor mechanical properties and limited self-healing ability hinder their potential as supporting materials. Furthermore, the absence of osteogenic and angiogenic properties significantly affect their application in bone regeneration. For injectable hydrogels, simulating natural bone tissue ECM presents an opportunity for developing innovative materials for bone repair. In this work, a strategy to prepare biomimetic nanofiber-reinforced dually cross-linked (DC) injectable hydrogels with self-healing, osteogenic and angiogenic properties was proposed. The PLGA/MDex/CaP@PBLG nanofiber hydrogels were crosslinked through two reversible dynamic interactions including Schiff base reaction and physical chelation, thereby demonstrating good self-healing property. Meanwhile, the incorporation of CaP@PBLG mineralized nanofibers and alendronate sodium (BP) grafted on PLGA could endow the hydrogels with favorable osteogenic function. Moreover, the introduction of antioxidant ferulic acid (FA) could significantly stimulate angiogenic activity of the hydrogels. The successful regeneration of cranial defects in rats demonstrated a potential application of PLGA/MDex/CaP@PBLG nanofiber hydrogels in the field of bone regeneration.

Autonomous Underwater Self-Healable Adhesive Elastomers Enabled by Dynamical Hydrophobic Phase-Separated Microdomains.

High-efficient underwater self-healing materials with reliable mechanical attributes hold great promise for applications in ocean explorations and diverse underwater operations. Nevertheless, achieving these functions in aquatic environments is challenging because the recombination of dynamic interactions will suffer from resistance to interfacial water molecules. Herein, an ultra-robust and all-environment stable self-healable polyurethane-amide supramolecular elastomer is developed through rational engineering of hydrophobic domains and multistrength hydrogen bonding interactions to provide mechanical and healing compatibility as well as efficient suppression of water ingress. The coupling of hydrophobic chains and hierarchical hydrogen bonds within a multiphase matrix self-assemble to generate dynamical hydrophobic hard-phase microdomains, which synergistically realize high stretchability (1601%), extreme toughness (87.1MJm-3), and outstanding capability to autonomous self-healing in various harsh aqueous conditions with an efficiency of 58% and healed strength of 12.7MPa underwater. Furthermore, the self-aggregation of hydrophobic clusters with sufficient dynamic interactions endows the resultant elastomer with effective instantaneous adhesion (6.2MPa, 941.9Nm-1) in extremely harsh aqueous conditions. It is revealed that the dynamical hydrophobic hard-phase microdomain composed of hydrophobic barriers and cooperative reversible interactions allows for regulating its mechanical enhancement and underwater self-healing efficiency, enabling the elastomers as intelligent sealing devices in marine applications.

Robust and highly proton conductive COF composite membranes for fuel cell and electrochemical hydrogen compression

Robust and highly conductive proton exchange membrane (PEM) is the unremitting pursuit of numerous electrochemical energy technologies such as fuel cell and the emerging electrochemical hydrogen compression. Ionic covalent organic framework nanosheets (iCONs) with long-range ordered nanochannels and abundant ionic groups show substantial potential as next-generation PEM materials. However, it is challenging to assemble iCONs into membranes with both robustness and flexibility due to the electrostatic repulsion and rigid framework. Herein, we propose a hydrogen-bond binding strategy to fabricate sulfonic iCON (SCON) composite membranes by co-assembling tannic acid (TA) nanoaggregates and SCONs. The abundant and dynamically reversible hydrogen-bond interactions introduced by TA nanoaggregates establish effective linkage between SCONs and allow some restricted movements, endowing membranes with remarkably improved mechanical properties. The stacked SCONs construct long-range ordered nanochannels with well-arranged sulfonic groups in membranes, and the hydrogen-bond networks further facilitate the proton transport through Grotthuss mechanism. Consequently, TA/SCON composite membranes displays significantly enhanced tensile strength of 101.9 MPa, good flexibility and high proton conductivity of 490.1 mS cm−1 at 80 °C and 100 % RH simultaneously. This hydrogen-bond binding strategy offers a promising approach to fabricate robust and highly conductive PEMs for various proton-conducting applications.

Versatile and recyclable double-network PVA/cellulose hydrogels for strain sensors and triboelectric nanogenerators under harsh conditions

Versatile and recyclable conductive hydrogels with long-term environmental adaptability and mechanical stability have attracted tremendous attention in wearable smart electronics. Here, double-network (DN) polyvinyl alcohol (PVA)/cellulose hydrogels were constructed after introducing a conductive rigid cellulose/Zn2+/Ca2+ network into a soft PVA/borax network. The resultant hydrogels possessed good mechanical and self-adhesive properties, along with transparency, recyclability, and remarkable resistance to freezing. They showed 30-day non-drying properties due to the presence of hygroscopic salts through a dynamic moisture adsorption and desorption process. Dehydrated hydrogels can return to their original states via self-regeneration under high relative humidity. Hydrogel-based strain sensors retained good sensitivity and a wide sensing range during the wide working temperature ranging from −40 °C to 50 °C and after recycling. Additionally, conductive hydrogels were integrated into triboelectric nanogenerators (TENGs) functioning as energy harvesters for powering electronics. TENGs retained stable electrical outputs even under harsh conditions and after recycling. Hydrogels were also assembled into flexible self-powered biomechanical sensors and tactile sensors. Thermally reversible interactions in composite hydrogels enabled their good recyclability, thereby reducing economic costs and environmental impacts caused by e-wastes. This work demonstrates the great potential of versatile and recyclable hydrogels with good environmental and mechanical stability in wearable smart electronics under harsh conditions.

Abstract 7141: The novel microtubule-destabilizing compound AUS_001 maintains unique binding to the colchicine site of tubulin and elicits reversible cellular effects relative to other anti-tubulin agents

Abstract Our previous work showed that the prenylated hydroxy-stilbene AUS_001 exerts a strong safety profile and potent anti-proliferative responses, as assessed in 30 types of cancer cell lines, stemming from its microtubule destabilization activity. The aim of the current study was to delineate the molecular mechanism of microtubule destabilization by AUS_001 and to provide insight into its high potency and low toxicity. Surface plasmon resonance (SPR) experiments revealed the direct interaction of AUS_001 with tubulin with an apparent equilibrium dissociation constant, Kd, of 2.13 × 10−5M. Size exclusion competition assays and an X-ray crystal structure of the tubulin-AUS_001 complex at 2.1 Å resolution establish ligand binding within the colchicine site on tubulin. Since colchicine-site ligands are well known to inhibit the curved-to-straight conformational transition of tubulin, which is an essential process for microtubule formation, these results readily explain the microtubule-destabilizing activity of the compound. Notably, while both combretastatin A4 (CA-4) and AUS_001 are both colchicine-site stilbene ligands, CA-4 binds in the cis configuration, while AUS_001 maintains a trans configuration leading to a substantially different pocket engagement. Comparison of the tubulin-AUS_001 complex structure with the ones of tubulin-colchicine and tubulin-plinabulin revealed that AUS_001 elicits different rearrangements in the T7 loop of β-tubulin versus colchicine and occupies a different zone of the pocket relative to plinabulin, further elaborating its unique binding properties. Interestingly, AUS_001 exhibits a higher relative affinity than colchicine itself, as assessed by i) an ultrafiltration-based tubulin-ligand release assay and ii) a radioligand colchicine competition assay. However, fitting steady state SPR data for AUS_001 binding to tubulin revealed fast association and dissociation rates and was indicative of reversible binding. The latter finding is corroborated by AUS_001-triggered reverse biological effects including morphological alterations, cell cycle G2/M arrest, and by a decrease of cell viability upon discontinuation of the drug treatment in glioma and pancreatic cancer cells. Conversely, colchicine, CA-4 or paclitaxel administered at the same doses as those applied for AUS_001 failed to reverse the drug-induced phenotypes upon removal resulting in sustained cytotoxicity. In conclusion, we fully characterized the unique binding mode of AUS_001 to the colchicine site of tubulin and elucidated the reversible nature of the target engagement. AUS_001 features a distinctive and reversible molecular interaction with tubulin which provides a plausible explanation for its favorable safety profile compared to other microtubule targeting agents. Citation Format: Herman Lelie, Yao-Chieh Chou, Alastair J. King, Zlata Boiarska, Andrea E. Prota, Michel O. Steinmetz, Marina Koutsioumpa. The novel microtubule-destabilizing compound AUS_001 maintains unique binding to the colchicine site of tubulin and elicits reversible cellular effects relative to other anti-tubulin agents [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7141.

Size effect of dynamic bioactive magnetic particles on regulated isolation of tumor cells

Circulating tumor cells (CTCs) are critical biomarkers in cancer metastasis, yet their isolation from the bloodstream remains a challenging task due to their low abundance. This study introduces a method for the efficient isolation of CTCs, utilizing dynamic biointerface-based magnetic particles (DBMPs), with a particular emphasis on the role of particle size. We have developed three distinct sizes DBMPs specifically tailored for effective CTCs interaction, leveraging the unique properties of polydopamine (PDA) coatings and phenylboronic acid (PBA)-modified capture peptides through reversible catechol-boronate interactions. Comparative analysis of DBMPs of varying sizes was assessed under uniform experimental conditions for their capture and release efficiencies. The findings reveal a clear distinction: smaller particles (DBMP1 and DBMP2) achieved greater efficiency in capturing CTCs, whereas the larger particles (DBMP3) were more effective in releasing them. This difference is ascribed to the varied interaction dynamics between the particles and CTCs. Furthermore, we have fine-tuned DBMP3 to optimize CTC capture while still maintaining a high efficiency in cell release. The integration of these DBMPs into a magnetic isolation framework is poised to significantly enhance CTCs isolation methods, marking a pivotal advancement in cancer diagnostics and management.

In Situ Grown Coordination-Supramolecular Layer Holding 3D Charged Channels for Highly Reversible Zn Anodes.

Dynamic reversible noncovalent interactions make supramolecular framework (SF) structures flexible and designable. A three-dimensional (3D) growth of such frameworks is beneficial to improve the structure stability while maintaining unique properties. Here, through the ionic interaction of the polyoxometalate cluster, coordination of zinc ions with cationic terpyridine, and hydrogen bonding of grafted carboxyl groups, the construction of a 3D SF at a well-crystallized state is realized. The framework can grow in situ on the Zn surface, further extending laterally into a full covering without defects. Relying on the dissolution and the postcoordination effects, the 3D SF layer is used as an artificial solid electrolyte interphase to improve the Zn-anode performance. The uniformly distributed clusters within nanosized pores create a negatively charged nanochannel, accelerating zinc ion transfer and homogenizing zinc deposition. The 3D SF/Zn symmetric cells demonstrate high stability for over 3000 h at a current density of 5 mA cm-2.