Observing the Dynamics of an Electrochemically Driven Active Material with Liquid Electron Microscopy.

Electrochemical liquid electron microscopy has revolutionized our understanding of nanomaterial dynamics by allowing for direct observation of their electrochemical production. This technique, primarily applied to inorganic materials, is now being used to explore the self-assembly dynamics of active molecular materials. Our study examines these dynamics across various scales, from the nanoscale behavior of individual fibers to the micrometer-scale hierarchical evolution of fiber clusters. To isolate the influences of the electron beam and electrical potential on material behavior, we conducted thorough beam-sample interaction analyses. Our findings reveal that the dynamics of these active materials at the nanoscale are shaped by their proximity to the electrode and the applied electrical current. By integrating electron microscopy observations with reaction-diffusion simulations, we uncover that local structures and their formation history play a crucial role in determining assembly rates. This suggests that the emergence of nonequilibrium structures can locally accelerate further structural development, offering insights into the behavior of active materials under electrochemical conditions.

Nanoantennas report dissipative assembly in oscillatory electric fields.

Understanding driving forces for dissipative, i.e., out of equilibrium, assembly of nanoparticles from colloidal solution at liquid-solid interfaces provides the ability to design external cues for reconfigurable device response. Here electrohydrodynamic flow (EHD) at an electrode-liquid interface is investigated as a dissipative driving force for tuning optical response. EHD results from an oscillatory electric field in a liquid cell between two electrodes and drives assembly of gold nanoparticles (NP) into two-dimensional clusters on electrode surfaces. Clusters are chemically crosslinked during assembly to freeze assemblies for electron microscopy characterization in order to understand how to 'nucleate' cluster formation. Electron microscopy images show deposition with a potential having an amplitude of 5 V and frequency of 100 Hz produces surfaces with isolated NP, which can seed EHD flow. A second deposition step at 5 V and 500 Hz produces a high density of quadramers on surfaces. When exciting near the local surface plasmon resonance of the Au NP clusters formed during assembly, Au NPs serve as in situ nanoantenna reporters of assembly and disassembly. Surface enhanced Raman scattering (SERS) measurements of Au NP capped with 4-mercaptobenzoic acid show order of magnitude signal enhancements occur during cluster formation in the presence of an oscillatory field, which occurs on a time scale of seconds. Confocal fluorescence spectroscopy is used to monitor the dissipative assembly of Au NP over multiple cycles. Results provide insight on how electrical stimuli and seeding local perturbations affects formation of NP clusters and resultant optical response provides insight on how to tune response of optically active surfaces.

A Vitrimer Acts as a Compatibilizer for Polyethylene and Polypropylene Blends.

Polymer compatibilization plays a critical role in achieving polymer blends with favorable mechanical properties and enabling efficient recycling of mixed plastic wastes. Nonetheless, traditional compatibilization methods often require tailored designs based on the specific chemical compositions of the blends. In this study, we propose a new approach for compatibilizing polymer blends using a dynamically crosslinked polymer network, known as vitrimers. By adding a relatively small amount (1-5 w/w%) of a vitrimer made of siloxane-crosslinked high-density polyethylene (HDPE), we successfully compatibilized unmodified HDPE and isotactic polypropylene (iPP). The vitrimer-compatibilized blend exhibited enhanced elongation at break (120 %) and smaller iPP domain sizes (0.4 µm) compared to the control blend (22 % elongation at break, 0.9 µm iPP droplet size). Moreover, the vitrimer-compatibilized blend showed significantly improved microphase stability during annealing at 180 °C. This straightforward method shows promise for applications across various polymer blend systems.

CryoEM reveals the complex self-assembly of a chemically driven disulfide hydrogel.

Inspired by the adaptability of biological materials, a variety of synthetic, chemically driven self-assembly processes have been developed that result in the transient formation of supramolecular structures. These structures form through two simultaneous reactions, forward and backward, which generate and consume a molecule that undergoes self-assembly. The dynamics of these assembly processes have been shown to differ from conventional thermodynamically stable molecular assemblies. However, the evolution of nanoscale morphologies in chemically driven self-assembly and how they compare to conventional assemblies has not been resolved. Here, we use a chemically driven redox system to separately carry out the forward and backward reactions. We analyze the forward and backward reactions both sequentially and synchronously with time-resolved cryogenic transmission electron microscopy (cryoEM). Quantitative image analysis shows that the synchronous process is more complex and heterogeneous than the sequential process. Our key finding is that a thermodynamically unstable stacked nanorod phase, briefly observed in the backward reaction, is sustained for ∼6 hours in the synchronous process. Kinetic Monte Carlo modeling show that the synchronous process is driven by multiple cycles of assembly and disassembly. The collective data suggest that chemically driven self-assembly can create sustained morphologies not seen in thermodynamically stable assemblies by kinetically stabilizing transient intermediates. This finding provides plausible design principles to develop and optimize supramolecular materials with novel properties.

Multiscale Molecular Dynamics Simulations of an Active Self-Assembling Material.

Inspired by the adaptability observed in biological materials, self-assembly processes have attracted significant interest for their potential to yield novel materials with unique properties. However, experimental methods have often fallen short in capturing the molecular details of the assembly process. In this study, we employ a multiscale molecular dynamics simulation approach, complemented by NMR quantification, to investigate the mechanism of self-assembly in a redox-fueled bioinspired system. Contrary to conventional assumptions, we have uncovered a significant role played by the monomer precursor in the assembly process, with its presence varying with concentration and the extent of conversion of the monomer to the dimer. Experimental confirmation through NMR quantification underscores the concentration-dependent incorporation of monomers into the fibrous structures. Furthermore, our simulations also shed light on the diverse intermolecular interactions, including T-shaped and parallel π stacking, as well as hydrogen bonds, in stabilizing the aggregates. Overall, the open conformation of the dimer is preferred within these aggregates. However, inside the aggregates, the distribution of conformations shifts slightly to the closed conformation compared to on the surface. These findings contribute to the growing field of bioinspired materials science by providing valuable mechanistic and structural insights to guide the design and development of self-assembling materials with biomimetic functionalities.

Fluoride-Catalyzed Siloxane Exchange as a Robust Dynamic Chemistry for High-Performance Vitrimers.

Sustainable development of new technologies requires materials having advanced physical and chemical properties while maintaining reprocessability and recyclability. Vitrimers are designed for this purpose; however, their dynamic covalent chemistries often have drawbacks or are limited to specialized polymers. Here, fluoride-catalyzed siloxane exchange is reported as an exceptionally robust chemistry for scalable production of high-performance vitrimers through industrial processing of commodity polymers such as poly(methyl methacrylate), polyethylene, and polypropylene. The vitrimers show improved resistance to creep, heat, oxidation, and hydrolysis, while maintaining excellent melt flow for processing and recycling. Furthermore, the siloxane exchange between different vitrimers during mechanical blending results in self-compatibilized blends without any compatibilizers. This offers a general, scalable method for producing sustainable high-performance vitrimers and a new strategy for recycling mixed plastic wastes.

Passive Automatic Switch Relying on Laplace Pressure for Efficient Underwater Low-Gas-Flux Bubble Energy Harvesting.

The buoyancy potential energy contained in bubbles released by subsea geological and biological activities represents a possible in situ energy source for underwater sensing and detection equipment. However, the low gas flux of the bubble seepages that exist widely on the seabed introduces severe challenges. Herein, a passive automatic switch relying on Laplace pressure is proposed for efficient energy harvesting from low-gas-flux bubbles. This switch has no moving mechanical parts; it uses the Laplace-pressure difference across a curved gas-liquid interface in a biconical channel as an invisible "microvalve". If there is mechanical equilibrium between the Laplace-pressure difference and the liquid-pressure difference, the microvalve will remain closed and prevent the release of bubbles as they continue to accumulate. After the accumulated gas reaches a threshold value, the microvalve will open automatically, and the gas will be released rapidly, relying on the positive feedback of interface mechanics. Using this device, the gas buoyancy potential energy entering the energy harvesting system per unit time can be increased by a factor of more than 30. Compared with a traditional bubble energy harvesting system without a switch, this system achieves a 19.55-fold increase in output power and a 5.16-fold enhancement in electrical energy production. The potential energy of ultralow flow rate bubbles (as low as 3.97 mL/min) is effectively collected. This work provides a new design philosophy for passive automatic-switching control of gas-liquid two-phase fluids, presenting an effective approach for harvesting of buoyancy potential energy from low-gas-flux bubble seepages. This opens a promising avenue for in situ energy supply for subsea scientific observation networks.

Waste-Free Fully Electrically Fueled Dissipative Self-Assembly System.

The importance and prevalence of energy-fueled active materials in living systems have inspired the design of synthetic active materials using various fuels. However, several major limitations of current designs remain to be addressed, such as the accumulation of chemical wastes during the process, unsustainable active behavior, and the lack of precise spatiotemporal control. Here, we demonstrate a fully electrically fueled (e-fueled) active self-assembly material that can overcome the aforementioned limitations. Using an electrochemical setup with dual electrocatalysts, the anodic oxidation of one electrocatalyst (ferrocyanide, [Fe(CN)6]4-) creates a positive fuel to activate the self-assembly, while simultaneously, the cathodic reduction of the other electrocatalyst (methyl viologen, [MV]2+) generates a negative fuel triggering fiber disassembly. Due to the fully catalytic nature for the reaction networks, this fully e-fueled active material system does not generate any chemical waste, can sustain active behavior for an extended period when the electrical potential is maintained, and provides spatiotemporal control.

Precise Control of Dissipative Self-assembly by Light and Electricity.

Nature-inspired synthetic dissipative self-assemblies have attracted much attention recently. However, it remains a major challenge to achieve precise control over dissipative supramolecular assembly structures and functions of self-contained systems. Here we combine light and electricity as two clean, and spatiotemporally addressable fuels to provide precise control over the morphology for dissipative self-assembly of a perylene bisimide glycine (PBIg) building block in a self-contained solution. In this design, electrochemical oxidation provides the positive fuel to activate PBIg self-assembly while photoreduction supplies the negative fuel to deactivate the system for disassembly. Through programming the two counteracting fuels, we demonstrated the control of PBIg self-assembly into a variety of assembly morphologies in a self-contained system. In addition, by exerting light and electrical dual fuels simultaneously, we could create an active homeostasis exhibiting dynamic instability, leading to morphological change to asymmetric assemblies with curvatures. Such precise control over self-assembly of self-contained systems may find future applications in programming complex active materials as well as formulating pharmaceutical reagents with desired morphologies.

Sugar-Fueled Dissipative Living Materials.

Dissipative behaviors in biology are fuel-driven processes controlled by living cells, and they shape the structural and functional complexities in biological materials. This concept has inspired the development of various forms of synthetic dissipative materials controlled by time-dependent consumption of chemical or physical fuels, such as reactive chemical species, light, and electricity. To date, synthetic living materials featuring dissipative behaviors directly controlled by the fuel consumption of their constituent cells is unprecedented. In this paper, we report a chemical fuel-driven dissipative behavior of living materials comprising Staphylococcus epidermidis and telechelic block copolymers. The macroscopic phase transition is controlled by d-glucose which serves a dual role of a competitive disassembling agent and a biological fuel source for living cells. Our work is a significant step toward constructing a synthetic dissipative living system and provides a new tool and knowledge to design emergent living materials.

Super-Aerophilic Biomimetic Cactus for Underwater Dispersed Microbubble Capture, Self-Transport, Coalescence, and Energy Harvesting.

Human ocean activities are inseparable from the supply of energy. The energy contained in the gas-phase components dispersed in seawater is a potential universal energy source for eupelagic or deep-sea equipment. However, the low energy density of bubbles dispersed in water introduces severe challenges to the potential energy harvesting of gas-phase components. Here, a super-aerophilic biomimetic cactus is developed for underwater dispersive microbubble capture and energy harvesting. The bubbles captured by the super-aerophilic biomimetic cactus spines, driven by the surface tension and liquid pressure, undergo automatic transport, coalescence, accumulation, and concentrated release. The formerly unavailable low-density dispersive surface free energy of the bubbles is converted into high-density concentrated gas buoyancy potential energy, thereby providing an energy source for underwater in situ electricity generation. Experiments show a continuous process of microbubble capture by the biomimetic cactus and demonstrate a 22.76-times increase in output power and a 3.56-times enhancement in electrical energy production compared with a conventional bubble energy harvesting device. The output energy density is 3.64 times that of the existing bubble energy generator. This work provides a novel approach for dispersive gas-phase potential energy harvesting in seawater, opening up promising prospects for wide-area in situ energy supply in underwater environments.

Facile Synthesis of Multifunctional Bioreducible Polymers for mRNA Delivery.

Bioreducible polymeric mRNA carriers are an emerging family of vectors for gene delivery and vaccine development. A few bioreducible systems have been generated through aqueous-phase ring-opening polymerization of lipoic acid derivatives, however this methodology limits hydrophobic group incorporation and functionality into resulting polymers. Herein, a poly(active ester)disulfide polymer is synthesized that can undergo facile aminolysis with amine-containing substrates under stoichiometric control and mild reaction conditions to yield a library of multifunctional polydisulfide polymers. Functionalized polydisulfide polymer species form stable mRNA-polymer nanoparticles for intracellular delivery of mRNAs in vitro. Alkyl-functionalized polydisulfide-RNA nanoparticles demonstrate rapid cellular uptake and excellent biodegradability when delivering EGFP and OVA mRNAs to cells in vitro. This streamlined polydisulfide synthesis provides a new facile methodology for accessing multifunctional bioreducible polymers as biomaterials for RNA delivery and other applications.

Electrically Fueled Active Supramolecular Materials.

Fuel-driven dissipative self-assemblies play essential roles in living systems, contributing both to their complex, dynamic structures and emergent functions. Several dissipative supramolecular materials have been created using chemicals or light as fuel. However, electrical energy, one of the most common energy sources, has remained unexplored for such purposes. Here, we demonstrate a new platform for creating active supramolecular materials using electrically fueled dissipative self-assembly. Through an electrochemical redox reaction network, a transient and highly active supramolecular assembly is achieved with rapid kinetics, directionality, and precise spatiotemporal control. As electronic signals are the default information carriers in modern technology, the described approach offers a potential opportunity to integrate active materials into electronic devices for bioelectronic applications.

Multifunctional Dendronized Polypeptides for Controlled Adjuvanticity.

Vaccination has been playing an important role in treating both infectious and cancerous diseases. Nevertheless, many diseases still lack proper vaccines due to the difficulty to generate sufficient amounts of antigen-specific antibodies or T cells. Adjuvants provide an important route to improve and direct immune responses. However, there are few adjuvants approved clinically and many of them lack the clear structure/adjuvanticity relationship. Here, we synthesized and evaluated a series of dendronized polypeptides (denpols) functionalized with varying tryptophan/histidine (W/H) molar ratios of 0/100, 25/75, 50/50, 75/25, and 100/0 as tunable synthetic adjuvants. The denpols showed structure-dependent inflammasome activation in THP1 monocytic cells and structure-related activation and antigen cross-presentation in vitro in bone marrow-derived dendritic cells. We used the denpols with bacterial pathogen Coxiella burnetii antigens in vivo, which showed both high and tunable adjuvating activities, as demonstrated by the antigen-specific antibody and T cell responses. The denpols are easy to make and scalable, biodegradable, and have highly adjustable chemical structures. Taken together, denpols show great potential as a new and versatile adjuvant platform that allows us to adjust adjuvanticity based on structure-activity correlation with the aim to fine-tune the immune response, thus advancing vaccine development.

Apatinib suppresses the migration, invasion and angiogenesis of hepatocellular carcinoma cells by blocking VEGF and PI3K/AKT signaling pathways.

Hepatocellular carcinoma (HCC) is a commonly diagnosed malignancy worldwide with poor prognosis and high metastasis and recurrence rates. Although apatinib has been demonstrated to have potential antitumor activity in multiple solid tumors, the underlying mechanism of apatinib in HCC treatment remains to be elucidated. In the present study, apatinib were used to treat HCC cells transfected with or without VEGFR2 overexpression vectors. The proliferation of HCC cells was detected by MTT assay. The migration and invasion of HCC cells were detected by wound healing assay and Transwell assay. The ability of angiogenesis of HCC cells were detected by tube formation assay. The related protein expression levels were detected by western blotting. The present study aims to investigate the effect and potential mechanism of apatinib on the migration, invasion and angiogenesis of HCC cells. It was found that apatinib treatment significantly inhibited the proliferation, migration and invasion of Hep3b cells and suppressed angiogenesis in HUVECs. In addition, apatinib inhibited the epithelial­mesenchymal transition of Hep3b cells by increasing the expression of the epithelial hallmarks E­cadherin and α­catenin and decreased the expression of the mesenchymal hallmarks N­cadherin and vimentin. These effects were associated with the downregulation of VEGF and VEGFR2 and suppression of the PI3K/AKT signaling pathway. Thus, apatinib inhibited cell migration, invasion and angiogenesis by blocking the VEGF and PI3K/AKT pathways, supporting an effective therapeutic strategy in the treatment of HCC.

Multivalent Peptide-Functionalized Bioreducible Polymers for Cellular Delivery of Various RNAs.

RNA-based therapeutics have garnered tremendous attention due to their potential to revolutionize protein replacement therapies, immunotherapy, and treatment of genetic disorders. The lack of safe and efficient RNA delivery methods has significantly hindered the clinical translation and widespread application of RNA-based therapeutics. With differing sizes and structures of therapeutic RNA molecules, a critical challenge of the field is to develop RNA delivery systems that accommodate these variations while retaining high biocompatibility and efficacy. In this study, we developed a series of multivalent peptide-functionalized bioreducible polymers (MPBP) as a safe and efficient delivery vehicle derived from a core polymer backbone for various RNA species. The facile synthesis of MPBPs from a single polymer backbone provides access to numerous polymers with diverse architectures that enable cellular delivery of different RNA cargos. Postfunctionalization with multifunctional peptides enables strong RNA complexation, enhanced cellular uptake, and facilitates endosomal escape of cargo. The high delivery efficiency and low cytotoxicity for various RNA-MPBP nanoparticles in multiple cell lines demonstrates that the MPBP approach is a novel promising vector strategy for future RNA delivery systems.

Direct Silyl Ether Metathesis for Vitrimers with Exceptional Thermal Stability.

Vitrimers are a new class of polymeric materials that simultaneously offer the desired physical properties of thermosets and malleability/reprocessability of thermoplastics. Despite significant progress being made in the field of vitrimers, there exists a critical need for the development of robust dynamic covalent chemistries for the production of strong and thermally stable vitrimers. In this work, we discovered a new silyl ether metathesis reaction and used it for the preparation of vitrimers with exceptional thermal stability. In small-molecule model studies, we observed that silyl ether motifs directly exchange under anhydrous conditions catalyzed by a Brønsted or Lewis acid catalyst. For initial vitrimer demonstration, a commodity polymer, poly(ethylene-co-vinyl alcohol) (PEOH), was silylated with trimethylsilyl (TMS) groups followed by cross-linking with a bis-silyl ether cross-linker. The resulting thermoset showed exceptional thermal stability while maintaining malleability/reprocessability at elevated temperatures. The vitrimer properties such as recyclability and stress relaxation at various temperatures were carefully investigated. The material was reprocessable at 150 °C while also exhibiting good creep resistance at temperatures below its melting transition (Tm). This work demonstrates the silyl ether metathesis reaction as a new, robust dynamic covalent chemistry to introduce plasticity, reprocessability, and recyclability to thermosets.

A Three-Armed Polymer with Tunable Self-Assembly and Self-Healing Properties Based on Benzene-1,3,5-tricarboxamide and Metal-Ligand Interactions.

The dynamic nature of supramolecules makes them useful in the fields of smart devices. The combination of multiple dynamic interactions in one material may bring some enhanced properties in mechanical property, self-healing property, or recyclability. Thus, it is significantly meaningful to design new materials with multi-dynamic bonds and clarify their bonding mechanisms. Here, a novel three-armed polymer based on benzene-1,3,5-tricarboxamide (BTA) is developed and the polymer could be further complexed by metal ions to form dynamic zinc-imidazole interactions. In this system, BTA is located in the center, and the ligand-functionalized monomer is copolymerized with n-butyl acrylate to form three chains. This is the first time BTA is introduced to a self-healing system to endow the polymer with assembly and self-healing properties. The composition, chemical structure, assembly behavior, mechanical properties, and self-healing properties of the polymer are investigated. It is revealed that the assembly behavior of the polymer depends on the BTA contents and time. The mechanical property can be easily tuned by ligand/metal ratio and is significantly adjusted by the polymer chain length and environment humidity. Long polymer chains not only contribute to good mechanical property but also promote the self-healing process due to the effective physical entanglement.

Correction to "Immunomodulation of the NLRP3 Inflammasome through Structure-Based Activator Design and Functional Regulation via Lysosomal Rupture".

[This corrects the article DOI: 10.1021/acscentsci.8b00218.].

Immunomodulation of the NLRP3 Inflammasome through Structure-Based Activator Design and Functional Regulation via Lysosomal Rupture.

The NLRP3 inflammasome plays a role in the inflammatory response to vaccines, in antimicrobial host defense, and in autoimmune diseases. However, its mechanism of action remains incompletely understood. NLRP3 has been shown to be activated by diverse stimuli including microbial toxins, ATP, particulate matter, etc. that activate multiple cellular processes. There have been two major challenges in translating inflammasome activators into controlled adjuvants. Both stem from their chemical and structural diversity. First, it is difficult to identify a minimum requirement for inflammasome activation. Second, no current activator can be tuned to generate a desired degree of activation. Thus, in order to design such immunomodulatory biomaterials, we developed a new tunable lysosomal rupture probe that leads to significant differences in inflammasome activation owing to structural changes as small as a single amino acid. Using these probes, we conduct experiments that suggest that rupturing lysosomes is a critical, initial step necessary to activate an inflammasome and that it precedes other pathways of activation. We demonstrate that each molecule differentially activates the inflammasome based solely on their degree of lysosomal rupture. We have employed this understanding of chemical control in structure-based design of immunomodulatory NLRP3 agonists on a semipredictive basis. This information may guide therapeutic interventions to prevent or mitigate lysosomal rupture and will also provide a predictive framework for dosable activation of the NLRP3 inflammasome for potential applications in vaccines and immunotherapies.