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Proteins form complexes through precise folding and interactions, which are crucial for biological processes. Understanding these mechanisms provides valuable biophysical insights and guides the design of biomimetic materials for applications in medicine, energy, and nanotechnology. Atomic force microscopy (AFM) is essential for studying protein assemblies and interactions in situ at various spatial and temporal scales. This review highlights recent advancements in AFM for elucidating protein structures, diffusions, interactions, phase transitions, and dynamics at solid‒liquid interfaces. It emphasizes the expanding role of AFM in exploring protein assembly and its implications for biomaterial and biomedical research.

An artificial chaperone can serve opposite roles, a catalyst at low dosage while an inhibitor at high dosage, in regulating the supramolecular polymerization of peptides. This system undergoes a cascading phase separation process, and the interplay and evolution of electrostatic and hydrophobic interactions between chaperones and peptides are the keys to achieving these processes.

Aggregation and aging of nanoparticle‒protein complexes at interfaces are resolved via evanescent-light scattering microscopy. Time- and space-resolved measurements by correlation functions show that the aging of such soft materials is out-of-equilibrium, stretched and compressed exponential decays can coexist in one aging process. Corona formation, inner stress, and interconnection are key for the aggregation and aging dynamics.

Payload-freeprotein nanoparticles (PNPs) wereself-assembled from purified silk fibroin (SF) with β-sheetstructures under the assistance of ethanol in aqueous media. The orallyadministered PNPs, without loading anything, are stable in the gastrointestinaltract (GIT) and can retain in the inflamed colon, modulate intestinalmicrobiome and metabolome, and effectively treat colitis without causingundesired side effects.

Peptide-mediated nanoparticle self-assembly uses diffusion-limited aggregation of silver nanoparticles to provide a scalable and tunable method for building hierarchal plasmonic fractal structures. By leveraging peptide sequences to control interparticle distance and material morphology, this approach simplifies synthesis and reveals insights into assembly mechanisms for applications in sensing and electronics.

This study identifies a novel small-molecule phase separation (PS) inhibitor 29 and a pathogenic factor GTP-binding nuclear protein Ran-like (NbRANL) in Nicotiana benthamiana. NbRANL promotes nucleocapsid protein (NP) PS. Compound 29 targets the intrinsically disordered regions of the NP and inhibits NbRANL expression, disrupting the PS and significantly suppressing tomato spotted wilt virus (TSWV) pathogenicity.

A novel DNA nanomachine (Cu@tFNAs-G-A NM) is constructed and exhibits the ability to effectively penetrate the BBB and selectively accumulate in tumor cells. Moreover, the Cu@tFNAs-G-A NM can react with tumor-overexpressed GSH and H₂O₂ to generate a large amount of •OH, thus leading to an effective CDT against GBM.

A self-aggregated, DNA-encoded plasmonic bubbles-driven SERS assay that leverages synergic plasmonic nanogaps and dual-target catalytic Raman enhancement to enable simultaneous, ultrasensitive, and specific detection of dual-miRNA for accurate cancer diagnosis.

Previous evidence suggests helicases regulate transcription. This study explores DHX36's transcriptional role using CUT&Tag to map binding sites in MCF-7 cells. AMUC-seq and AID systems identify DHX36-regulated genes. Results show G4s enrich at DHX36 targets, primarily in active regions. DHX36 interacts with G4s from oncogenes, implicating its role in transcription modulation.

On the basis of revealing the ternary interaction mechanism of multiple biomacromolecules (amylose [AM], lauric acid [LA], and β-lactoglobulin [βLG]) through experiments and simulation calculations, a thermally controlled hierarchical strategy was firstly reported for self-assembly of AM–LA–βLG complex into uniform-sized nanospheres with well-defined crystalline structure and stability. These nanospheres were substantially resistant to amylolysis and presented great fermentation functions by gut microbiota, including production of short-chain fatty acids and regulating the bacterial composition and diversity.

A minimum secondary structured RCA technique (MSS-RCA) is introduced by designing a unique circular template with significantly enhanced amplification efficiency and sensitivity. By incorporating an invertase probe, MSS-RCA detected HPV16 E6/E7 nucleic acid with high sensitivity and accuracy using a personal glucose meter, offering a valuable tool for cervical cancer screening in point-of-care.

Organoids have emerged as promising in vitro models, but current research primarily centers on single organoids, missing crucial inter-organ communication. This review explores diverse aspects including materials design, culture environment manipulation, and organoid morphology control to establish and enhance multi-organoid systems for more comprehensive and physiologically relevant in vitro modeling of complex human physiology.

We rationally designed the water-soluble recombinant keratins using QTY code to enhance their homotypic self-assembly performance in the aqueous environment, which was a great help to form a gel at the wound sites using one kind of keratin rather than two heteropolymerics of specific keratin pairs. Furthermore, QTY variant keratins displayed superior hemostatic and wound healing activities compared to native recombinant keratins.

The rise in antibiotic resistance shows ongoing pressure to implant placement and can lead to implant failure, especially dental implants. Numerous strategies are applied to reduce/prevent peri-implantitis, including coating peptide antibiotics. Here we summarise the current strategies of coating AMPs, for example chemical or self-assembly approaches, onto dental implants with multi-functional properties to enhance osteoblast growth and prevent bacterial infections.

Aggregation-induced emission artificial enzyme (AIEzyme) with DNase-like activity is designed by the coordination polymerization of AIE ligands and Zr⁴⁺ centers. AIEzyme shows long-acting hydrolysis for eDNA with good penetrability in biofilm and realizes superbug-infected wound healing under only one dose. The structural rigidity-stabilized fluorescence of AIEzyme facilitates the study on its penetrability and residual amount during anti-biofilm process monitoring.

The viscosity sensitivity of rotor-based fluorophores can be regulated by the installation of intramolecular hydrogen bonds at excited states.

This work presents an ingenious design to create oil-repellent packaging materials and tableware toward detergent-free water-cleaning pathways, thereby greatly reducing the negative environmental impact of surfactant emissions. The key point of this report is that the introduction of an amyloid-like phase-transitioned lysozyme intermediate layer into a cellulose nanocrystal coating can rapidly modify any target surface to create a robust underwater oil-repellent state.

Protein amyloid aggregate plays important roles in both physiological processes and pathological diseases. In this review, the structural basis of self-assembly of amyloid fibrillar aggregation, and how the different structures of amyloid aggregates determine their distinct pathological or physiological activities are elucidated.

A novel multi-interaction cooperative nanochaperone (multi-co-nChap) is designed to regulating protein folding including facilitate de novo protein folding and protect native proteins from thermally induced misfolding and aggregation. The corona electrostatic attraction facilitates the diffusion of clients into the hydrophobic microdomains, while the shell electrostatic and hydrophobic interaction balances the capture and release of clients.

This review places an emphasis on the introduction of the programmable DNA-functionalized plasmonic nanoassemblies as SERS sensors for environmental analysis, where the specifically designed DNA acts as both structure basis and functional unit, combining the specificity of DNA recognition and the sensitivity of SERS detection via modulating the assembly of plasmonic nanoparticles.

BODIPY-based molecular rotor fluorophores are developed to visualize protein aggregation via the increase of fluorescence intensity and lifetime. Combined with fluorescence lifetime imaging, this dual signal probe is used to quantify micro-viscosity changes in different forms of protein aggregates.

Ion behaviors in an aggregated state like in the confined nanochannel are of researchers’ particular interest. Inspired by the ion transport in ion channels of neurons, this could be further applied to develop artificial neurons and neural networks based on the nanofluidics.

Recent advances on imaging and patterning of individual DNA molecules by atomic force microscopy are highlighted. Aggregation-induced crowding interactions, specifically the hybridization and self-assembly behaviors of surface-immobilized DNA capture probes in close proximity are reviewed and discussed. A single-molecule level understanding of structure–function relationship at surfaces paves the way toward rational engineering of DNA-based sensors and microarrays.

Denatured proteins show new vitality for hollow structures with versatile functions. Denatured bovine serum albumin can trigger an unusual biomineralization for the simple, green, and shape-controllable synthesis of GeOx hollow microsphere (HMS). GeOx HMS shows great application potential for intelligent gut-targeted pesticide delivery, label-free COVID-19 immunosensors, and nonenzymatic H₂O₂ sensors under physiological conditions at negative potentials.

The diagram illustrates the four possible outcomes upon mixing two immiscible droplets, which are dictated by the interfacial tension between the two droplets and between the droplets and the solvent phase. Generalizations of this principle can be used to understand biocondensate organization and its connection with the interactions among the molecular components.

The precise control of cell–cell aggregation is not only vital for the cell biological field but also important for bioengineering field. In this review, we summarize the recent strategies using chemical and biological molecules to achieve the programmable regulation of cell–cell aggregations. We discuss the advantage and disadvantage of recent approaches, and talk about the possible development of the technology in this filed in future.

Spherical nucleic acids are prepared by densely coated nucleic acids on the nanoparticle core. These organized nucleotide aggregates present significantly different biological properties compared to their linear counterparts, enabling advances in biosensing, bioimaging, and biomedicine.

With careful design, nucleic acid–based aggregates can be constructed by tiles-based ligation, hybridization, or RCA/RCT reaction. Nucleic acid linkers can be integrated to other nanomaterials to fabricate nucleic acid–assisted aggregates. In this minireview, the recent advances of these aggregates for various biomedical applications, such as drug delivery, bioimaging, biosensing, cell analysis, and combined cancer therapy, are summarized.

The development of efficient fluorescent probes is a prerequisite for successful fluorescence imaging-guided surgery. This review provides a brief overview of the molecular designs of the targeted fluorescent probes under clinical evaluation, followed by recent advances in the field of NIR-II fluorescence imaging. In addition, key considerations concerning the design of fluorescent probes for clinical translation are discussed.

Photoacoustic imaging (PAI) has emerged as a promising technique for real-time detection and diagnosis of brain-related pathologies with the advantages of deep penetration and high resolution. This article discusses the latest developments of nanoparticles as PA contrast agents specifically designed for PAI of brain related disorders.

The direction of evolution is from simple to complex. Most components in a cell are interdependent in their mode of action, aggregating into a complex structure to function. Research on different intracellular complexes will facilitate the prevention and treatment of various diseases. Here, protein aggregates PML-NBs, protein-nucleic acid aggregates ribosomes, and protein-nucleic acid-lipid aggregates exosomes are listed and discussed, respectively.

Enzyme-activatable optical probes are emerging as a new class of promising imaging tools for precise diagnosis of diseases at early stage with high target-to-background ratio, remarkably improved sensitivity, and dramatically enhanced specificity. This review briefly summarizes the most recent advances in this booming area, and analyzes the molecular design and working mechanism to offer insights into their biomedical applications.

DNA-organic molecular amphiphiles are synthesized from hydrophilic DNA and hydrophobic organic molecules with various topologic structures. These DNA amphiphiles can self-assemble into the designable nanostructures as well as induce the formation of the hierarchical aggregates.

According to the different synthesis methods which result in various structures and properties of AIEgen-lipids, the structures are summarized into four kinds: core-shell, inserted, imbedded and like-lipid structures. The AIE molecule in monodisperse state presents no emission but aggregate shows high fluorescence intensity, as well as distinct ROS generation performance.

DNA nanostructures have extraordinary advantages in placing fluorescent molecules with near-atomic scale precision and controllable number. In this review, we summarize the recent progress of DNA nanostructure-encoded fluorescent barcodes and discuss the intermolecular photophysical interactions of dyes on the DNA template. Finally, the applications of fluorescent barcodes in biosensing and bioimaging are reviewed.