Interface of biomolecular condensates modulates redox reactions

Chem, Journal Year: 2023, Volume and Issue: 9(6), P. 1594 - 1609

Published: April 28, 2023

Language: Английский

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Dipeptide coacervates as artificial membraneless organelles for bioorthogonal catalysis

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Jan. 2, 2024

Abstract Artificial organelles can manipulate cellular functions and introduce non-biological processes into cells. Coacervate droplets have emerged as a close analog of membraneless organelles. Their biomimetic properties, such molecular crowding selective partitioning, make them promising components for designing cell-like materials. However, their use artificial has been limited by complex structure, control over internal microenvironment inherent colloidal instability. Here we report the design dipeptide coacervates that exhibit enhanced stability, biocompatibility, hydrophobic microenvironment. The character facilitates encapsulation species, including transition metal-based catalysts, enhancing efficiency in aqueous environments. Dipeptide carrying catalyst are incorporated active cells trigger an chemical reaction. development with opens alternative avenue field materials applications catalysis synthetic biology.

Language: Английский

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Fundamental Aspects of Phase-Separated Biomolecular Condensates

Chemical Reviews, Journal Year: 2024, Volume and Issue: 124(13), P. 8550 - 8595

Published: June 17, 2024

Biomolecular condensates, formed through phase separation, are upending our understanding in much of molecular, cell, and developmental biology. There is an urgent need to elucidate the physicochemical foundations behaviors properties biomolecular condensates. Here we aim fill this by writing a comprehensive, critical, accessible review on fundamental aspects phase-separated We introduce relevant theoretical background, present basis for computation experimental measurement condensate properties, give mechanistic interpretations terms interactions at molecular residue levels.

Language: Английский

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De novo design of modular protein hydrogels with programmable intra- and extracellular viscoelasticity

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(6)

Published: Jan. 30, 2024

Relating the macroscopic properties of protein-based materials to their underlying component microstructure is an outstanding challenge. Here, we exploit computational design specify size, flexibility, and valency de novo protein building blocks, as well interaction dynamics between them, investigate how molecular parameters govern viscoelasticity resultant hydrogels. We construct gel systems from pairs symmetric homo-oligomers, each comprising 2, 5, 24, or 120 individual components, that are crosslinked either physically covalently into idealized step-growth biopolymer networks. Through rheological assessment, find covalent linkage multifunctional precursors yields hydrogels whose depends on crosslink length constituent blocks. In contrast, reversibly crosslinking homo-oligomeric components with a computationally designed heterodimer results in viscoelastic biomaterials exhibiting fluid-like under rest low shear, but solid-like behavior at higher frequencies. Exploiting unique genetic encodability these materials, demonstrate assembly networks within living mammalian cells show via fluorescence recovery after photobleaching (FRAP) mechanical can be tuned intracellularly manner similar formulations formed extracellularly. anticipate ability modularly systematically program designer could have broad utility biomedicine, applications tissue engineering, therapeutic delivery, synthetic biology.

Language: Английский

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Molecular determinants of condensate composition

Molecular Cell, Journal Year: 2025, Volume and Issue: 85(2), P. 290 - 308

Published: Jan. 1, 2025

Language: Английский

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Biomolecular condensates regulate cellular electrochemical equilibria

Cell, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 1, 2024

Language: Английский

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Designer peptide–DNA cytoskeletons regulate the function of synthetic cells

Nature Chemistry, Journal Year: 2024, Volume and Issue: 16(8), P. 1229 - 1239

Published: April 23, 2024

The bottom-up engineering of artificial cells requires a reconfigurable cytoskeleton that can organize at distinct locations and dynamically modulate its structural mechanical properties. Here, inspired by the vast array actin-binding proteins their ability to reversibly crosslink or bundle filaments, we have designed library peptide-DNA crosslinkers varying in length, valency geometry. Peptide filaments conjoint through DNA hybridization give rise tactoid-shaped bundles with tunable aspect ratios mechanics. When confined cell-sized water-in-oil droplets, crosslinker design guides localization cytoskeletal structures cortex within lumen synthetic cells. spatial arrangement regulates passive diffusion payloads droplets complementary handles allow for reversible recruitment release on off cytoskeleton. Heat-induced reconfiguration architectures triggers shape deformations regulated melting temperatures. Altogether, modular is powerful strategy towards assembly

Language: Английский

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Biomolecular condensates can function as inherent catalysts

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: July 10, 2024

We report the discovery that chemical reactions such as ATP hydrolysis can be catalyzed by condensates formed intrinsically disordered proteins (IDPs), which themselves lack any intrinsic ability to function enzymes. This inherent catalytic feature of derives from electrochemical environments and electric fields at interfaces are direct consequences phase separation. The we studied were capable catalyzing diverse reactions, including radical-dependent breakdown whereby fully decomposes adenine multiple carbohydrates. distinguishes naturally occurring ATPases, only catalyze dephosphorylation ATP. Interphase interfacial properties tuned via sequence design, thus enabling control over catalysis through sequence-dependent features condensates. Incorporation hydrolase-like synthetic into live cells enables activation transcriptional circuits depend on products reactions. Inherent functions condensates, emergent separation, likely affect metabolic regulation in cells.

Language: Английский

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Biomolecular condensates with complex architectures via controlled nucleation

Nature Chemical Engineering, Journal Year: 2024, Volume and Issue: unknown

Published: June 10, 2024

Language: Английский

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Co-transcriptional production of programmable RNA condensates and synthetic organelles

Nature Nanotechnology, Journal Year: 2024, Volume and Issue: 19(11), P. 1665 - 1673

Published: July 30, 2024

Abstract Condensation of RNA and proteins is central to cellular functions, the ability program it would be valuable in synthetic biology cell science. Here we introduce a modular platform for engineering condensates from tailor-made, branched nanostructures that fold assemble co-transcriptionally. Up three orthogonal can form simultaneously selectively accumulate fluorophores through embedded fluorescent light-up aptamers. The expressed within cells produce membrane-less organelles with controlled number relative size, showing capture using selective protein-binding affinity between otherwise modulated by introducing dedicated linker constructs, enabling production bi-phasic prescribed degree interphase mixing diverse morphologies. situ expression programmable could underpin spatial organization functionalities both biological cells.

Language: Английский

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