Peptide-Mediated Liquid-Liquid Phase Separation and Biomolecular Condensates

Soft Matter, Год журнала: 2025, Номер 21(10), С. 1781 - 1812

Опубликована: Янв. 1, 2025

Peptide-mediated liquid–liquid phase separation (LLPS) underpins the formation of dynamic biomolecular condensates, regulated by diverse molecular interactions, and highlights potential applications in drug delivery synthetic biology.

Язык: Английский

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Structured protein domains enter the spotlight: modulators of biomolecular condensate form and function

Trends in Biochemical Sciences, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Язык: Английский

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Peptide Coacervates: Formation, Mechanism, and Biological Applications

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

Опубликована: Апрель 30, 2025

Biomolecular coacervates, dynamic compartments formed via liquid-liquid phase separation (LLPS), are essential for orchestrating intracellular processes and have emerged as versatile tools in bioengineering. Peptides, with their modular amino acid sequences, exhibit unique potential coacervate design due to ability undergo LLPS while offering precise control over molecular architecture environmental responsiveness. Their simplicity, synthetic accessibility, tunability make peptide-based coacervates particularly attractive biomedical materials applications. However, the formation stability of these systems depend on a delicate balance intrinsic factors (e.g., sequence charge, hydrophobicity, chain length) extrinsic conditions pH, ionic strength, temperature), necessitating deeper understanding interplay. This review synthesizes recent advances mechanisms driving peptide coacervation, emphasizing how cues govern behavior. We further highlight groundbreaking applications, from drug delivery platforms protocell mimics, discuss strategies translate mechanistic insights into functional materials. By bridging fundamental principles innovative this work aims accelerate development programmable, multifunctional systems, roadmap next-generation biochemical technologies.

Язык: Английский

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pH-Sulfate Synergy Regulates Processing and Mechanics of Mussel Byssus Protein Condensates

Chemistry of Materials, Год журнала: 2025, Номер unknown

Опубликована: Янв. 30, 2025

Язык: Английский

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Transition-State-Dependent Spontaneous Generation of Reactive Oxygen Species by Aβ Assemblies Encodes a Self-Regulated Positive Feedback Loop for Aggregate Formation

Journal of the American Chemical Society, Год журнала: 2025, Номер unknown

Опубликована: Фев. 25, 2025

Amyloid-β (Aβ) peptides exhibit distinct biological activities across multiple physical length scales, including monomers, oligomers, and fibrils. The transition from Aβ monomers to pathological aggregates correlates with the emergence of chemical toxicity, which plays a critical role in progression neurodegenerative disorders. However, relationship between state assemblies their toxicity remains poorly understood. Here, we show that can spontaneously generate reactive oxygen species (ROS) through transition-state-specific inherent nonenzymatic redox activity. During initial intermediate oligomers or condensates final fibrils, interfacial electrochemical environments emerge vary at liquid–liquid liquid–solid interfaces. Determined by vibrational Stark effect using electronic pre-resonance stimulated Raman scattering microscopy, field such is on order 10 MV/cm. Interfacial activity, depends state, modulate spontaneous oxidation hydroxide anions, leads formation hydroxyl radicals. Interestingly, this activity modifies composition establishes self-regulated positive feedback loop accelerates aggregation promotes fibril formation, represents new functioning mechanism beyond cross-linking. Leveraging mechanistic insight, identified small molecules capable disrupting scavenging radicals perturbing interface, thereby inhibiting formation. Our findings provide model neurotoxicity reveal interfaces modulating dynamics biomolecular assemblies. These results offer novel framework for therapeutic intervention Alzheimer's disease related

Язык: Английский

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In Situ Lighting-Up Near-Infrared Metabolic Probes for Super-Resolution Imaging of Glycogen

ACS Sensors, Год журнала: 2025, Номер unknown

Опубликована: Март 10, 2025

High-fidelity tracking of glycogen dynamics in living biosystems is critical for exploring the biological role metabolism diseases. However, situ information on state mainly relies a glucose uptake fluorescence probe 2-NBDG, which has proven to be extremely limited owing "always-on" fluorescence, short emission wavelength, and low signal-to-noise (S/N) ratio. Herein, we first time demonstrate metabolic-activated off-on through covalently attaching molecular rotor with hydrophilic at C-2 position guarantee good miscibility complete fluorescence-off before metabolic incorporation into particles. The Glycogen-Red achieves negligible background (1/30 times than 2-NBDG) an ultrahigh S/N ratio (61-fold lighting-up near-infrared (NIR) biosynthesis. Notably, our unique characteristic bypassing washing steps, offering powerful toolbox real-time biosynthesis super-resolution mapping structures cells.

Язык: Английский

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Gel-to-Coacervate Transition in Peptide/HA Complexes for MMP-9-Activated Penetration into Tumor Spheroids

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

Опубликована: Март 15, 2025

Short phase-separating peptides serve as liquid-based vehicles due to their remarkable fluidity and cell permeability, holding great promise in diffusion-limited applications such intracellular drug delivery or penetration into deep-seated tumors. However, tuning the phase stability phase-transition sensitivity of these coacervates response specific pathological signals remains a significant challenge. To tackle this challenge, study presents peptide/hyaluronic acid (HA) complex coacervate system, which undergoes solid-to-coacervate transition upon exposure matrix metalloproteinase 9 (MMP-9). By harnessing disease-relevant enzyme, overexpressed ovarian tumor microenvironment, we further demonstrate improved infiltration Hey cells spheroids. These observations highlight feasibility modulating behaviors advanced functions through sequence-specific monomer design, offering practical strategy for on-target medicine

Язык: Английский

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Probing the Formation and Liquid-to-Solid Transition of FUS Condensates via the Lifetimes of Fluorescent Proteins

The Journal of Physical Chemistry Letters, Год журнала: 2025, Номер unknown, С. 3553 - 3561

Опубликована: Март 31, 2025

Liquid–liquid phase separation (LLPS) of biomolecules is a fundamental cellular process that essential for maintaining homeostasis and facilitating biochemical activities. On the other hand, aberrant alters condensate fluidity causes transition from liquid-like condensates to solid-like condensates, which may lead formation pathological aggregations often observed in neurodegenerative diseases. Condensate usually assessed by fluorescence recovery after photobleaching. Here, we reveal lifetimes several fluorescent proteins are sensitive LLPS liquid-to-solid transition. Furthermore, identify key residues regulate sensitivity toward separation. Thus, apply lifetime imaging microscopy (FLIM) visualize living cells, demonstrating FLIM nondestructive method tracking changes real time.

Язык: Английский

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Salt-Bridge-Mediated Coacervate-to-Vesicle Transformation in Arginine-Rich Coacervates

ACS Nano, Год журнала: 2025, Номер unknown

Опубликована: Апрель 22, 2025

Polypeptide-based liquid-liquid phase separation (LLPS) has received considerable attention as it governs the formation of membraneless organelles in cells. However, detailed mechanistic understanding how one most prevalent cationic amino acids proteins, arginine, interacts with various biomolecules to induce and undergo morphogenesis remains be resolved. Herein, we report behavior transformation arginine-rich coacervates into vesicular structures upon introducing polyphosphates. Transformation vesicles was shown occur independent initial anionic counterparts driven by salt-bridge interactions between guanidinium groups arginine residues phosphates. We also investigate role intermolecular forces ionic effects on morphological further exploit their potential assembly artificial tissue-like constructs. Overall, our findings underpin a unifying principle for vesicle from potency reconstituting hierarchical biological microcompartments.

Язык: Английский

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pH-sulfate synergy regulates processing and mechanics of mussel byssus protein condensates

Опубликована: Авг. 1, 2024

Fluid protein condensates are used as precursor phases for fabricating extracellular protein-based materials including elastin, spider silk, and mussel byssus. The byssus, utilized by mussels anchoring in marine environments, consists of tough, self-healing adhesive fibers. Byssus formation involves the secretion condensate droplets under acidic conditions that subsequently solidify basic seawater conditions. We currently have a poor understanding physicochemical triggers molecular-level interactions at play, particular role pH sulfate anions previously identified during native fabrication. Here, we investigated sulfate-dependent structural mechanical response made from recombinant byssus (mfp-1) using optical tweezers microrheology, FRAP, confocal Raman spectroscopy, NMR, cryo-EM. found concentration increased, viscoelastic became more rigid presence ions compared with chloride ions, consistent spectroscopic analysis indicating different molecular these chemical These studies highlight crucial interplay between tuning viscoelasticity via control intermolecular interactions, providing insights into natural process relevance bio-inspired processing sustainable plastics tissue engineering.

Язык: Английский

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