Endogenous capsid-forming protein ARC for self-assembling nanoparticle vaccines.

The application of nanoscale scaffolds has become a promising strategy in vaccine design, with protein-based nanoparticles offering desirable avenues for the biocompatible and efficient delivery of antigens. Here, we presented a novel endogenous capsid-forming protein, activated-regulated cytoskeleton-associated protein (ARC), which could be engineered through the plug-and-play strategy (SpyCatcher3/SpyTag3) for multivalent display of antigens. Combined with the self-assembly capacity and flexible modularity of ARC, ARC-based vaccines elicited robust immune responses against Mpox or SARS-CoV-2, comparable to those induced by ferritin-based vaccines. Additionally, ARC-based nanoparticles functioned as immunostimulants, efficiently stimulating dendritic cells and facilitating germinal center responses. Even without adjuvants, ARC-based vaccines generated protective immune responses in a lethal challenge model. Hence, this study showed the feasibility of ARC as a novel protein-based nanocarrier for multivalent surface display of pathogenic antigens and demonstrated the potential of exploiting recombinant mammalian retrovirus-like protein as a delivery vehicle for bioactive molecules.

Single-Nanoparticle Electrochemical Collision for Monitoring Self-Assembly of Thiol Molecules on Au Nanoparticles.

A precise understanding of the self-assembly kinetics of small molecules on nanoparticles (NPs) can give greater control over the size and architecture of the functionalized NPs. Herein, a single-nanoparticle electrochemical collision (SNEC)-based method was developed to monitor the self-assembly processes of 6-mercapto-1-hexanol (6-MCH) and 1-hexanethiol (MCH) on Au NPs at the single-particle level, and to investigate the self-assembly kinetics exactly. Results showed that the self-assembly processes of both consisted of rapid adsorption and slow recombination. However, the adsorption rate of MCH was significantly lower than that of 6-MCH due to the poorer polarity. Also noteworthy is that the rapid adsorption of 6-MCH on Au NPs conformed to the Langmuir model of diffusion control. Hence, the proposed SNEC-based method could serve as a complementary method to research the self-assembly mechanism of functionalized NPs.

A Review on the Rheological Properties of Single Amino Acids and Short Dipeptide Gels.

Self-assembled peptide-based hydrogels have attracted considerable interest from the research community. Particularly, low molecular weight gelators (LMWGs) consisting of amino acids and short peptides are highly suitable for biological applications owing to their facile synthesis and scalability, as well as their biocompatibility, biodegradability, and stability in physiological conditions. However, challenges in understanding the structure-property relationship and lack of design rules hinder the development of new gelators with the required properties for several applications. Hereby, in the plethora of peptide-based gelators, this review discusses the mechanical properties of single amino acid and dipeptide-based hydrogels. A mutual analysis of these systems allows us to highlight the relationship between the gel mechanical properties and amino acid sequence, preparation methods, or N capping groups. Additionally, recent advancements in the tuning of the gels' rheological properties are reviewed. In this way, the present review aims to help bridge the knowledge gap between structure and mechanical properties, easing the selection or design of peptides with the required properties for biological applications.

Elastin-Derived Peptide-Based Hydrogels as a Potential Drug Delivery System.

A peptide-based hydrogel sequence was computationally predicted from the Ala-rich cross-linked domains of elastin. Three candidate peptides were subsequently synthesised and characterised as potential drug delivery vehicles. The elastin-derived peptides are Fmoc-FFAAAAKAA-NH2, Fmoc-FFAAAKAA-NH2, and Fmoc-FFAAAKAAA-NH2. All three peptide sequences were able to self-assemble into nanofibers. However, only the first two could form hydrogels, which are preferred as delivery systems compared to solutions. Both of these peptides also exhibited favourable nanofiber lengths of at least 1.86 and 4.57 µm, respectively, which are beneficial for the successful delivery and stability of drugs. The shorter fibre lengths of the third peptide (maximum 0.649 µm) could have inhibited their self-assembly into the three-dimensional networks crucial to hydrogel formation.

Chirality in Singlet Fission: Controlling Singlet Fission in Aqueous Nanoparticles of Tetracenedicarboxylic Acid Ion Pairs.

The singlet fission characteristics of aqueous nanoparticles, self-assembled from ion pairs of tetracene dicarboxylic acid and various amines with or without chirality, are thoroughly investigated. The structure of the ammonium molecule, the counterion, is found to play a decisive role in determining the molecular orientation of the ion pairs and its regularity, spectroscopic properties, the strength of the intermolecular coupling between the tetracene chromophores, and the consequent singlet fission process. Using chiral amines has led to the formation of crystalline nanosheets and efficient singlet fission with a triplet quantum yield as high as 133% ±20% and a rate constant of 6.99 × 109 s-1. The chiral ion pairs also provide a separation channel to free triplets with yields as high as 33% ±10%. In contrast, nanoparticles with achiral counterions do not show singlet fission, which gave low or high fluorescence quantum yields depending on the size of the counterions. The racemic ion pair produces a correlated triplet pair intermediate by singlet fission, but no decorrelation into two free triplets is observed, as triplet-triplet annihilation dominates. The introduction of chirality enables higher control over orientation and singlet fission in self-assembled chromophores. It provides new design guidelines for singlet fission materials.

Chirality and Curvature on Protein Adsorption and Osteogenesis.

Here we designed enantiomeric lipid-mimetic glutamic acid derivatives (L/D-UG) and investigated their self-assembled chiral nanostructures and performance with the protein adsorption as well as the osteogenesis. It was found that L or D-UG can self-assemble into vesicle bilayers and two-dimensional (2D) nanocrystals via a kinetic and thermodynamic control, respectively. These chiral vesicles and 2D crystals showed differentiated adsorption of proteins by their curvature and chirality. Specifically, fibronectin constituted by L-amino acids adsorbed preferentially on L-UG 2D crystal in a semi-random pattern and L-2D nanocrystal show as the most effective structures to promote bone regeneration. The controlled vesicle and 2D crystal assemblies with different chirality and curvature helps to clarify their determine roles in protein adsorption and osteogenesis.

A ß-Lactamase Responsive Peptide Inhibits MRSA Infection through Self-Assembled Nanonet.

Gram-positive S. aureus is one of the leading pathogens for death associated with antimicrobial resistance. The ß-lactamase (Bla) secreted by methicillin-resistant S. aureus (MRSA) hydrolyzes nearly all ß-lactam antibiotics, leaving only a few antibiotics available for the clinical treatment of MRSA infections. Thereby, a Bla-responsive peptide (BLAP) is designed here with the capacity of inhibiting MRSA infection through mimicking the host defense mechanism of human defensin-6. The BLAP comprising a self-assembling peptide sequence can respond specifically to the secreted Bla and assemble in situ surrounding MRSA. The assembled nanofibrous network is able to trap MRSA, preventing its invasion into the host cells effectively. As a consequence, the intramuscular injection of BLAP significantly restricted bacterial infection and abscess formation in mice. The biomimetic BLAP holds great potential for the efficient treatment of drug-resistant gram-positive bacterial infections.

The Synthesis of Functionalized Carbonized Polymer Dots via Reversible Assembly of Oligomers for Anti-Counterfeiting, Catalysis, and Gas storage.

Carbonized polymer dots (CPDs) have shown exceptional potential across a wide range of applications. However, their practical utilization is significantly greatly impeded by the lack of precise control over their structures and functionalities. Consequently, the development of controlled synthesis strategies for CPDs with well-defined structures and tailored functionalities remains a critical challenge in the field. Here, the controlled synthesis of functional CPDs with reversible assembly properties via airflow-assisted melt polymerization, followed by a one-step post-synthetic doping strategy, is reported. This synthetic approach achieves high product yield, uniform and tunable structures, as well as customized functionalities including solid-state emission, enhanced catalytic performance (3.5-45 times higher than conventional methods), and selective gas storage in the resulting CPDs. The ability to tailor the properties of CPDs through controlled synthesis opens up new opportunities for their practical application in photocatalysis and gas storage.

Self-assembled dipeptide confined in covalent organic polymers for fluorescence sensing of tryptamine in fermented meat products.

Diphenylalanine(FF)-Zn self-assembly (FS) confined in covalent organic polymers (FS@COPs) with efficient fluorescence was synthesized for fluorescence sensing of biogenic amines, which was one of the most important indicators for monitoring food freshness. FS@COPs combined excellent biodegradability of self-assembled dipeptide with chemical stability, porosity and targeted site recognition of COPs. With an optimal excitation wavelength of 360 nm and an optimal emission wavelength of 450 nm, FS@COPs could be used as fluorescence probes to rapidly visualize and highly sensitive determination of tryptamine (Try) within 15 min, and the linear range was from 40 to 900 µg L-1 with a detection limit of 63.08 µg kg-1. Importantly, the FS@COPs showed a high fluorescence quantum yield of 11.28%, and good stability, solubility, and selectivity, which could successfully achieve the rapid, accurate and highly sensitive identification of Try. Furthermore, we revealed the mechanism of FS@COPs for fluorescence sensing of targets. The FS@COPs system was applied to the fluorescence sensing of Try in real samples and showed satisfactory accuracy of 93.02%-105.25%.

Programmable Reconfiguration of Supramolecular Bottlebrush Block Copolymers: From Solution Self-Assembly to Co-Crystallization-Assistant Self-Assembly.

Achieving structural reconfiguration of supramolecular bottlebrush block copolymers toward topological engineering is of particular interest but challenging. Here, we address the creation of supramolecular architectures to discover how assembled topology influences the structured aggregates, combining hydrogen-bonded (H-bonded) bottlebrush block copolymers and electrostatic interaction induced polymer/inorganic eutectics. We first design H-bonding linear-brush block copolymer P(NBDAP-co-NBC)-b-P(NBPEO), bearing linear block P(NBDAP-co-NBC) (poly(norbornene-terminated diaminopyridine-co-norbornene-terminated hexane)) with pendant H-bonding DAP (diaminopyridine) motifs, and PEO (poly(ethylene oxide)) densely grafted P(NBPEO) brush block. Thanks to H-bonding association between DAP and thymine (Thy), incorporation of Thy-functionalized polystyrene (Thy-PS) enables solution self-assembly and formation of H-bonded bottlebrush block copolymers, generating augmented nanospheres with increasing Thy-PS amount. Noteworthy that integration of inorganic cluster silicotungstic acid (STA) to P(NBC-co-NBDAP)-b-P(NBPEO), endows the formation of PEO/STA eutectic core. Therefore, co-crystallization-assistant self-assembly at the interfaces of polymeric, inorganic and supramolecular chemistry is realized, reflecting multi-stage morphology transformation from hexagonal platelets, needle-like, curved rod-like micelles, finally to end-to-end closed rings, by gradually increasing Thy-PS while fixing STA content. Interestingly, such solution self-assembly to co-crystallization-assistant self-assembly strategy not only endows unique nanostructure transition, also induce in-to-out switch of PS domains. These findings clearly provide unique methodology towards programmable fabrication of geometrical objects promising in smart materials.

Room-Temperature Liquid Crystalline Tetraphenylethylene-Surfactant Complex with Chiral Supramolecular Structure and Tunable Circularly Polarized Luminescence.

A novel room-temperature liquid crystal of tetraphenylethylene derivative (TPE-DHAB) was synthesized using an ionic self-assembly strategy. The TPE-DHAB complex exhibits typical aggregation-induced emission properties and a unique helical supramolecular structure. Moreover, the generation and handedness inversion of circularly polarized luminescence (CPL) can be achieved through further chiral solvation, providing a facile approach to fabricate room-temperature liquid crystalline materials with controllable supramolecular structures and tunable CPL properties through a synergistic strategy of ionic self-assembly and chiral solvation process.

Size-Dependent Magnetic Responsiveness of a Photonic Crystal of Graphene Oxide Nanosheets.

A magnetically responsive photonic crystal of colloidal nanosheets can exhibit a controllable structural color, offering diverse potential applications. In this study, we systematically investigated how the lateral sizes of graphene oxide (GO) nanosheets affect their magnetic responsiveness in a photonic system. Contrary to the prediction that larger lateral sizes of nanosheets would be more responsive to an applied magnetic field based on the magnetic energy of anisotropic materials, we discovered that GO nanosheets with larger lateral sizes in the photonic system scarcely responded to a 12 T magnetic field. The lack of magnetic response may be due to the strongly restricted rotational motion of GO nanosheets by mutual electrostatic forces. In contrast, GO nanosheets with medium lateral sizes readily responded to the 12 T magnetic field, forming a uniaxially oriented structure that resulted in a vivid structural color. However, smaller GO nanosheets displayed a less vivid structural color, possibly because of less structural ordering of GO nanosheets. Finally, we found that the photonic crystal of GO nanosheets with optimized lateral sizes responded effectively to the 12 T magnetic field across various GO concentrations, resulting in a vivid and tunable structural color.

Unraveling the Source of Self-Induced Diastereomeric Anisochronism in Chiral Dipeptides.

Mastering of analytical methods for accurate quantitative determinations of enantiomeric excess is a crucial aspect in asymmetric catalysis, chiral synthesis, and pharmaceutical applications. In this context, the phenomenon of Self-Induced Diastereomeric Anisochronism (SIDA) can be exploited in NMR spectroscopy for accurate determinations of enantiomeric composition, without using a chiral auxiliary that could interfere with the spectroscopic investigation. This phenomenon can be particularly useful for improving the quantitative analysis of mixtures with low enantiomeric excesses, where direct integration of signals can be tricky. Here, we describe a novel analysis protocol to correctly determine the enantiomeric composition of scalemic mixtures and investigate the thermodynamic and stereochemical features at the basis of SIDA. Dipeptide derivatives were chosen as substrates for this study, given their central role in drug design. By integrating the experiments with a conformational stochastic search that includes entropic contributions, we provide valuable information on the dimerization thermodynamics, the nature of non-covalent interactions leading to self-association, and the differences in the chemical environment responsible for the anisochrony, highlighting the importance of different stereochemical arrangement and tight association for the distinction between homochiral and heterochiral adducts. An important role played by the counterion was pointed out by computational studies.

Multiscale Tunable Nanorings Based on Bi-Component Micellar-Configuration-Transformation Induced by Hydrophobicity.

Ringy nanostructures are amazing materials, displaying unique optical, magnetic, and electronic properties highly related to their dimensions. A strategy capable of continuously tailoring the diameter of nanorings is the key to elucidating their structure-function relationship. Herein, a method of bi-component micellar-configuration-transformation induced by hydrophobicity for the synthesis of nanorings with diameters ranging from submicron (≈143 nm) to micron (≈4.8 µm) and their carbonaceous analogs is established. Remarkably, the nanorings fabricated with this liquid phase strategy achieve the record for the largest diameter span. Through varying the molecular lengths of fatty alcohols and copolymers, shortening the molecular length of fatty alcohol can swell the primary micelles, improve the exposure of hydrophobic component and boost the assembly kinetics for ultra-large nanorings is shown here. On the other hand, shortening the molecular length of the copolymer will give rise to ultra-small nanorings by reducing the size of primary micelles and shortening the assembly time. When assembling the nanorings into monolayer arrays and then depositing Au, such substrate displays enhanced surface-enhanced Raman scattering (SERS) performance. This research develops a facile method for the controllable synthesis of ringy materials with multiscale tunable diameters and may inspire more interesting applications in physics, optical, and sensors.

Chemically Tagging Cargo for Specific Packaging inside and on the Surface of Virus-like Particles.

Virus-like particles (VLPs) have untapped potential for packaging and delivery of macromolecular cargo. To be a broadly useful platform, there needs to be a strategy for attaching macromolecules to the inside or the outside of the VLP with minimal modification of the platform or cargo. Here, we repurpose antiviral compounds that bind to hepatitis B virus (HBV) capsids to create a chemical tag to noncovalently attach cargo to the VLP. Our tag consists of a capsid assembly modulator, HAP13, connected to a linker terminating in maleimide. Our cargo is a green fluorescent protein (GFP) with a single addressable cysteine, a feature that can be engineered in many proteins. The HAP-GFP construct maintained HAP's intrinsic ability to bind HBV capsids and accelerate assembly. We investigated the capacity of HAP-GFP to coassemble with HBV capsid protein and bind to preassembled capsids. HAP-GFP binding was concentration-dependent, sensitive to capsid stability, and dependent on linker length. Long linkers had the greatest activity to bind capsids, while short linkers impeded assembly and damaged intact capsids. In coassembly reactions, >20 HAP-GFP molecules were presented on the outside and inside of the capsid, concentrating the cargo by more than 100-fold compared to bulk solution. We also tested an HAP-GFP with a cleavable linker so that external GFP molecules could be removed, resulting in exclusive internal packaging. These results demonstrate a generalizable strategy for attaching cargo to a VLP, supporting development of HBV as a modular VLP platform.

Robust Multifunctional Ultrathin 2 Nanometer Organic Nanofibers.

Ultrathin organic nanofibers (UTONFs) represent an emerging class of nanomaterials as they carry a set of favorable attributes, including ultrahigh specific surface area, lightweight, and mechanical flexibility, over inorganic counterparts, for use in biomedicine and nanotechnology. However, precise synthesis of uniform UTONFs (diameter ≤ 2 nm) with tailored functionalities remained challenging. Herein, we report robust multifunctional UTONFs using hydrophobic interaction-driven self-assembly of amphiphilic alternating peptoids containing hydrophobic photoresponsive azobenzene and hydrophilic hydroxyl moieties periodically arranged along the peptoid backbone. Notably, the as-crafted UTONFs are approximately 2 nm in diameter and tens of micrometers in length (an aspect ratio, AR, of ∼10000), exemplifying the UTONFs with the smallest diameter yielded via self-assembly. Intriguingly, UTONFs were disassembled into short-segmented nanofibers and controllably reassembled into UTONFs, resembling "step-growth polymerization". Photoisomerization of azobenzene moieties leads to reversible transformation between UTONFs and spherical micelles. Such meticulously engineered UTONFs demonstrate potential for catalysis, bioimaging, and antibacterial therapeutics. Our study highlights the significance of the rational design of amphiphiles containing alternating hydrophobic and hydrophilic moieties in constructing otherwise unattainable extremely thin UTONFs with ultrahigh AR and stimuli-responsive functionalities for energy and bionanotechnology.

Self-assembled high-entropy Prussian blue analogue nanosheets enabling efficient sodium storage.

High entropy material (HEM) has emerged as an appealing material platform for various applications, and specifically, the electrochemical performances of HEM could be further improved through self-assembled structure design. However, it remains a big challenge to construct such high-entropy self-assemblies primarily due to the compositional complexity. Herein, we propose a bottom-up directional freezing route to self-assemble high-entropy hydrosols into porous nanosheets. Taking Prussian blue analogue (PBA) as an example, the simultaneous coordination-substitution reactions yield stable high-entropy PBA hydrosols. During subsequent directional freezing process, the anisotropic growth of ice crystals could guide the two-dimensional confined assembly of colloidal nanoparticles, resulting in high-entropy PBA nanosheets (HE-PBA NSs). Thanks to the high-entropy and self-assembled structure design, the HE-PBA NSs manifests markedly enhanced sodium storage kinetics and performances in comparison with medium/low entropy nanosheets and high entropy nanoparticles.

Chameleonic Cages: Encapsulation of Anionic, Neutral, and Cationic Guest Species within [Fe4L4]8+ Tetrahedral Cages Synthesised from the tris(4-aminophenyl)phosphate pro-Ligand.

An adaptable Fe(II) tetrahedral cage, [Fe4L4][BF4]8 (L = tris(4-(((E)-pyridin-2-ylmethylene)amino)phenyl) phosphate), has been synthesised via self-assembly. By modulating the orientation of its pendant P=O groups, the cage was found to be capable of encapsulating anionic, neutral, and cationic guests, which was confirmed in the solid state via single-crystal X-ray diffraction (SCXRD) and in solution by high-resolution mass spectroscopy (HR-MS), as well as by NMR (1H, 19F, 31P) studies where possible.

Mechanochemical Diversity in Block Copolymers.

Covalent polymer chains are known to undergo mechanochemical events when subjected to mechanical forces. Such force-coupled reactions, like C-C bond scission in homopolymers, typically occur in a non-selective manner but with a higher probability at the mid-chain. In contrast, block copolymers (BCPs), composed of two or more chemically distinct chains linked by covalent bonds, have recently been shown to exhibit significantly different mechanochemical reactivities and selectivities. These differences may be attributable to the atypical conformations adopted by their chains, compared to the regular random coil. Beyond individual molecules, when BCPs self-assemble into ordered aggregates in solution, the non-covalent interactions between the chains lead to meaningful acceleration in the activation of embedded force-sensitive motifs. Furthermore, the microphase segregation of BCPs in bulk creates periodically dispersed polydomains, locking the blocks in specific conformations which have also been shown to affect their mechanochemical reactivity, with different morphologies influencing reactivity to varying extents. This review summarizes the studies of mechanochemistry in BCPs over the past two decades, from the molecular level to assemblies, and up to bulk materials.

Supramolecular J- and H-aggregation of Napthalimide-conjugated Dipeptide in Mixed-solvent Systems and Its Application in Cell Imaging.

In this work, a core substituted NMI-conjugated dipeptide (4MNLV) was extensively studied in mixed solvent systems to explore the polarity effect on the self-assembly pattern and their photophysical property. 4MNLV adopted a J- or H- type aggregation pattern depending upon the polarity index of the solvent system chosen. The self-assembly process was achieved through the anti-solvent effect. UV-vis study suggested that if the stock solution of 4MNLV was diluted with a relatively more polar solvent (compared to the stock solvent), then the system acquired J- type of aggregation pattern by showing a red-shift in their absorption maxima (λmax). Conversely, when the stock was diluted by a relatively less polar solvent, H-type of aggregation was observed where blue shift of λmax was noticed. The emission spectra and the lifetime of the self-assembled materials were also influenced by the chosen solvent system. The chirotopic behaviour of these self-assembled materials was studied through CD spectroscopy. Morphological study indicated the formation of helical nanofibrillar structures. The bright green fluorescence of these highly biocompatible naphthalimide-peptide conjugate was used for cell imaging application, indicating its futuristic scope.