Coacervates Composed of Low‐Molecular‐Weight Compounds– Molecular Design, Stimuli Responsiveness, Confined Reaction

Advanced Biology, Год журнала: 2025, Номер unknown

Опубликована: Фев. 12, 2025

The discovery of coacervation within living cells through liquid-liquid phase separation has inspired scientists to investigate its fundamental principles and significance. Indeed, coacervates composed low-molecular-weight compounds based on supramolecular strategy can offer valuable models for biomolecular condensates useful tools. This mini-review highlights recent findings advances in (artificial condensates), primarily compounds, with focuses their molecular design, stimuli responsiveness, controlled reactions or leading the coacervates.

Язык: Английский

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Functional Biomaterials Derived from Protein Liquid–Liquid Phase Separation and Liquid‐to‐Solid Transition

Advanced Materials, Год журнала: 2025, Номер unknown

Опубликована: Фев. 9, 2025

Protein phase transitions play a vital role in both cellular functions and pathogenesis. Dispersed proteins can undergo liquid-liquid separation to form condensates, process that is reversible highly regulated within cells. The formation physicochemical properties of these such as composition, viscosity, multiphase miscibility, are precisely modulated fulfill specific biological functions. However, protein condensates further liquid-to-solid state, forming β-sheet-rich aggregates may disrupt function lead diseases. While this phenomenon crucial for processes has significant implications neurodegenerative diseases, the behavior naturally derived or engineered polypeptides also presents opportunities developing high-performance, multifunctional materials at various scales. Additionally, unique molecular recruitment capabilities inspire innovative advancements biomaterial design applications drug discovery, delivery, biosynthesis. This work highlights recent progress understanding mechanisms underlying behavior, particularly how it responds internal changes external physical stimuli. Furthermore, fabrication from diverse sources through controlled demonstrated.

Язык: Английский

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Long non‐coding RNAs as key regulators of neurodegenerative protein aggregation

Alzheimer s & Dementia, Год журнала: 2025, Номер 21(2)

Опубликована: Фев. 1, 2025

Abstract The characteristic events in neurodegenerative diseases (NDDs) encompass protein misfolding, aggregation, accumulation, and their related cellular dysfunction, synaptic function loss. While distinct proteins are implicated the pathological processes of different NDDs, process misfolding aggregation remains notably similar across various conditions. Specifically, undergo into beta‐folded (β‐folded) conformation, resulting formation insoluble amyloid proteins. Despite advancements comprehending certain facets this intricate remain incompletely elucidated. In recent years, concept that long non‐coding RNAs (lncRNAs) contribute to has gained recognition. LncRNAs influence aggregates by facilitating overexpression through regulation gene transcription translation, inhibiting degradation via lysosomal autophagic pathways, targeting aberrant modifications phase transitions A better understanding relationship between lncRNAs is an important step dissecting underlying molecular mechanisms will discovery new therapeutic targets strategies. Highlights NDDs marked leading dysfunction loss function. being involved β‐folded conformations forming consistent role attention, as they regulate inhibit degradation, target modifications. Understanding link crucial for uncovering developing targets.

Язык: Английский

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Probing Noncovalent Interactions by Fast Magic‐Angle Spinning NMR at 100 kHz and More

ChemPhysChem, Год журнала: 2024, Номер unknown

Опубликована: Авг. 12, 2024

Abstract Noncovalent interactions are the basis for a large number of chemical and biological molecular‐recognition processes, such as those occurring in supramolecular chemistry, catalysis, solid‐state reactions mechanochemistry, protein folding, protein‐nucleic acid binding, biomolecular phase separation processes. In this perspective article, some recent developments probing noncovalent by proton‐detected Nuclear Magnetic Resonance (NMR) spectroscopy at Magic‐Angle Spinning (MAS) frequencies 100 kHz more reviewed. The development MAS rotors with decreasing outer diameters, combined superconducting magnets operating high static magnetic‐field strengths up to 28.2 T (1200 MHz proton Larmor frequency) improves resolution sensitivity NMR, which is fundamental requirement shedding light on solids. examples reported article range from binding ATP‐fueled motor proteins hydrogen‐π interaction calixarene‐lanthanide complex.

Язык: Английский

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Liquid-liquid crystalline phase separation of spider silk proteins

Communications Chemistry, Год журнала: 2024, Номер 7(1)

Опубликована: Ноя. 12, 2024

Liquid-liquid phase separation (LLPS) of proteins can be considered an intermediate solubility regime between disperse solutions and solid fibers. While LLPS has been described for several pathogenic amyloids, recent evidence suggests that it is similarly relevant functional amyloids. Here, we review the links spider silk (spidroins) its role in spinning process. Major ampullate spidroins undergo mediated by stickers spacers their repeat regions. During spinning, droplets shift from liquid to crystalline states. Shear force, altered ion composition, pH changes cause micelle-like spidroin assemblies form increasingly ordered liquid-crystalline phase. Interactions polyalanine regions ultimately yield characteristic β-crystalline structure mature dragline Based on these findings, hypothesize liquid-liquid (LLCPS) describe molecular macroscopic features transitions major during speculate whether other types may use a similar mechanism convert dope fiber.

Язык: Английский

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Deciphering the Seed Size-Dependent Cellular Internalization Mechanism for α-Synuclein Fibrils

Biochemistry, Год журнала: 2025, Номер 64(2), С. 377 - 400

Опубликована: Янв. 6, 2025

Aggregation of α-synuclein (α-Syn) and Lewy body (LB) formation are the key pathological events implicated in Parkinson's disease (PD) that spread a prion-like manner. However, biophysical structural characteristics toxic α-Syn species molecular drive early propagation amyloids manner remain elusive. We used neuronal cell model to demonstrate size-dependent native biological activities fibril seeds. Biophysical characterization seeds generated by controlled fragmentation indicated increased leads reduction size, correlating directly with extent events. Although size-based complexity amyloid fibrils modulates their amplification pathways, it remains unclear how variability seed size dictates its specific uptake mechanism into cells. The present study elucidates internalization is regulated Further, we endocytic pathways (dynamin-dependent clathrin/caveolin-mediated) more prominent for differential short compared longer counterparts. This preference might contribute enhanced transcellular Overall, suggests physical dimension significantly influences cellular responses initiation progression PD.

Язык: Английский

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Coalescence-Driven Local Crowding Promotes Liquid-to-Solid-Like Phase Transition in a Homogeneous and Heterogeneous Droplet Assembly: Regulatory Role of Ligands

Langmuir, Год журнала: 2025, Номер unknown

Опубликована: Апрель 14, 2025

Liquid-to-solid-like phase transition (LSPT) of disordered proteins via metastable liquid-like droplets is a well-documented phenomenon in biology and linked to many pathological conditions including neurodegenerative diseases. However, very less known about the early microscopic events transient intermediates involved irreversible protein aggregation functional globular proteins. Herein, using range spectroscopic techniques, we show that LSPT protein, human serum albumin (HSA), exclusively driven by spontaneous coalescence involving various temporal manner. We interdroplet communication essential for both initial growth amorphous aggregates within individual droplets, which subsequently transform amyloid-like fibrils. Immobilized neither any nucleation nor upon aging. Moreover, found exchange materials with dilute dispersed has negligible influence on HSA. Our findings reveal interfacial properties effectively modulate feasibility kinetics HSA ligand binding, suggesting possible regulatory mechanism cells utilize control dynamics LSPT. Furthermore, dynamic heterogeneous droplet assembly two proteins, transferrin (Tf), an intriguing fused where solid-like phases coexist same droplet, eventually mixed fibrillar assembly. These insights not only highlight importance interactions behind biomolecules but also showcase its adverse effect structure function other crowded

Язык: Английский

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Dynamic Flow-Assisted Nanoarchitectonics

ACS Applied Materials & Interfaces, Год журнала: 2025, Номер unknown

Опубликована: Апрель 21, 2025

The solution to societal problems such as energy, environmental, and biomedical issues lies in the development of functional material systems with capacity address these problems. In course human development, we are entering a new era which nanostructure control is considered major materials. concept nanoarchitectonics particularly significant this regard, it comprehensively promotes further nanotechnology its fusion materials chemistry. integration nanoscale phenomena macroscopic actions imperative for practical production structural precision. This review focuses on dynamic flow-assisted nanoarchitectonics, wherein explore organization structures by external mechanical stimuli, predominantly fluid flow. then proceeds select some examples divide them into categories purpose discussion: (i) natural flow, (ii) flow or stress created artificial equipment devices (forced flow), (iii) at specific field, namely interfaces, that is, layer-by-layer (LbL) assembly LB method. final perspective section discusses future research directions requirements nanoarchitectonics. meaningful effective use science set be area focus future, poised play role achieving objective.

Язык: Английский

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Liquid-liquid phase separation: a new perspective on respiratory diseases

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Сен. 26, 2024

Liquid-liquid phase separation (LLPS) is integral to various biological processes, facilitating signal transduction by creating a condensed, membrane-less environment that plays crucial roles in diverse physiological and pathological processes. Recent evidence has underscored the significance of LLPS human health disease. However, its implications respiratory diseases remain poorly understood. This review explores current insights into mechanisms LLPS, focusing particularly on relevance diseases, aiming deepen our understanding propose new paradigm for studying this context.

Язык: Английский

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Catalytic Assembly of Peptides Mediated by Complex Coacervates

ACS Nano, Год журнала: 2025, Номер unknown

Опубликована: Янв. 9, 2025

The assembly of peptides is generally mediated by liquid–liquid phase separation, which enables control over kinetics, final structure, and functions peptide-based supramolecular materials. Modulating separation can alter the kinetics changing solvents or introducing external fields. Herein, we demonstrate that be effectively catalyzed complex coacervates. negatively charged sodium alginate (SA) form coacervates with positively KLVFFAE (Aβ16–22, abbreviated as KE) peptide, thereby lowering nucleation barrier promoting peptide. As binding affinity SA-KE dosage SA decrease, system shifts from a relatively inefficient template-induced to highly efficient catalytic before ultimately reverting slow spontaneous assembly. Therefore, both well stoichiometry do not follow intuitive rule "more better", but rather there exists an optimal value maximizes rate

Язык: Английский

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