ArticleJournal of the American Chemical Society2024
Reversible Disulfide Bond Cross-Links as Tunable Levers of Phase Separation in Designer Biomolecular Condensates.
Article in Journal of the American Chemical Society, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- Closed-Loop Recyclable Solid Polymer Electrolytes via Dynamic Lipoate Cross-Linking.Angewandte Chemie (International ed. in English) · 2026Article
- Reversible Redox-Responsive Peptide Condensates With RNA.Chembiochem : a European journal of chemical biology · 2026Article
- Amphiphilic Lipid-Polymer Triblock Architectures as Nanocarriers for Therapeutic Delivery.ACS omega · 2026Article
- Diastereomeric Configuration Modulates Liquid-Liquid Phase Separation and Catalysis in Minimalist Dipeptide Coacervates.Angewandte Chemie (International ed. in English) · 2026Article
- Multiaxial Biophysical Control of Oncogenic Phase Separation by Indoleamines: A Proof-of-Concept Synthesis of Landscape-Level Regulation.Journal of pineal research · 2026Review
- Programmable Coacervates Based on Minimalist Sticker-Spacer Frameworks: Chemical Design, Functions, and Emerging Applications.ACS applied materials & interfaces · 2026Review
- Dilute but Dense - Reversible Crosslinking Enables Water-Rich (Bio)polymer Condensates.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- A Mini-Spidroin Forms High-Performance Artificial Spider Silk via Edge-Cysteine-Locked β-Sheet Assembly.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Site-specific methionine oxidation alters structure and phase separation of TDP-43 C-terminal domain.bioRxiv : the preprint server for biology · 2025Article
- Missense mutations in intrinsically disordered protein regions link pathogenicity and phase separation.The Journal of biological chemistry · 2025Article
- Disulfide cross-linked redox-sensitive peptide condensates are efficient cell delivery vehicles of molecular cargo.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Microscopy-based techniques for studying the material properties of biomolecular condensates in the cellular environment.Biophysical reviews · 2025Review
- Combating Reactive Oxygen Species (ROS) with Antioxidant Supramolecular Polymers.ACS applied materials & interfaces · 2025Article
- Disulfide cross-linked redox-sensitive peptide condensates are efficient cell delivery vehicles of molecular cargo.bioRxiv : the preprint server for biology · 2025Article
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Authors and funding
10 authors.
Funding
Abstract
Biomolecular condensates (BCs) are membraneless hubs enriched with proteins and nucleic acids that have emerged as important players in many cellular functions. Uncovering the sequence determinants of proteins for phase separation is essential in understanding the biophysical and biochemical properties of BCs. Despite significant discoveries in the past decade, the role of cysteine residues in BC formation and dissolution has remained unknown. Here, to uncover the involvement of disulfide cross-links and their redox sensitivity in BCs, we designed a "stickers and spacers" model of phase-separating peptides interspersed with cysteines. Through biophysical investigations, we learned that cysteines promote liquid-liquid phase separation in oxidizing conditions and perpetuate liquid condensates through disulfide cross-links, which can be reversibly tuned with redox chemistry. By varying the composition of cysteines, subtle but distinct changes in the viscoelastic behavior of the condensates were observed. Empirically, we conclude that cysteines function neither as stickers nor spacers but as covalent nodes to lower the effective concentrations for sticker interactions and inhibit system-spanning percolation networks. Together, we unmask the possible role of cysteines in the formation of biomolecular condensates and their potential use as tunable covalent cross-linkers in developing redox-sensitive viscoelastic materials.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.