Phase Transitions of Associative Biomacromolecules

Chemical Reviews, Journal Year: 2023, Volume and Issue: 123(14), P. 8945 - 8987

Published: March 7, 2023

Multivalent proteins and nucleic acids, collectively referred to as multivalent associative biomacromolecules, provide the driving forces for formation compositional regulation of biomolecular condensates. Here, we review key concepts phase transitions aqueous solutions specifically that include folded domains intrinsically disordered regions. The these systems come under rubric coupled segregative transitions. underlying processes are presented, their relevance condensates is discussed.

Language: Английский

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Macromolecular condensation organizes nucleolar sub-phases to set up a pH gradient

Cell, Journal Year: 2024, Volume and Issue: 187(8), P. 1889 - 1906.e24

Published: March 18, 2024

Nucleoli are multicomponent condensates defined by coexisting sub-phases. We identified distinct intrinsically disordered regions (IDRs), including acidic (D/E) tracts and K-blocks interspersed E-rich regions, as defining features of nucleolar proteins. show that the localization preferences proteins determined their IDRs types RNA or DNA binding domains they encompass. In vitro reconstitutions studies in cells showed how condensation, which combines complex coacervation components, contributes to organization. D/E contribute lowering pH co-condensates formed with RNAs vitro. cells, this sets up a gradient between nucleoli nucleoplasm. By contrast, juxta-nucleolar bodies, have different macromolecular compositions, featuring protein very charge profiles, values equivalent higher than Our findings compositional specificities generate physicochemical properties for condensates.

Language: Английский

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Liquid spherical shells are a non-equilibrium steady state of active droplets

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Oct. 17, 2023

Liquid-liquid phase separation yields spherical droplets that eventually coarsen to one large, stable droplet governed by the principle of minimal free energy. In chemically fueled separation, formation phase-separating molecules is coupled a fuel-driven, non-equilibrium reaction cycle. It thus dissipative structures sustained continuous fuel conversion. Such are ubiquitous in biology but poorly understood as they thermodynamics. Here, we bridge gap between passive, close-to-equilibrium, and active, with separation. We observe spherical, active can undergo morphological transition into liquid, shell. demonstrate mechanism related gradients short-lived material. characterize how far out equilibrium shell state chemical power necessary sustain it. Our work suggests alternative avenues for assembling complex morphologies, which might already be exploited form membraneless organelles cells.

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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Emergent microenvironments of nucleoli

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

Published: March 5, 2024

In higher eukaryotes, the nucleolus harbors at least three sub-phases that facilitate multiple functionalities including ribosome biogenesis. The prominent coexisting are fibrillar center (FC), dense component (DFC), and granular (GC). Here, we review recent efforts in profiling sub-phase compositions shed light on types of physicochemical properties emerge from compositional biases territorial organization specific macromolecules. We highlight roles played by molecular grammars which refers to protein sequence features substrate binding domains, intrinsically disordered regions, multivalence these distinct domains / regions. introduce concept a barcode emergent nucleoli. Although our knowledge full remains incomplete, hope prompts investigations into undiscovered engenders an appreciation for how why unique microenvironments control biochemical reactions

Language: Английский

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Biomolecular condensates form spatially inhomogeneous network fluids

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

Published: April 22, 2024

Abstract The functions of biomolecular condensates are thought to be influenced by their material properties, and these will determined the internal organization molecules within condensates. However, structural characterizations challenging, rarely reported. Here, we deploy a combination small angle neutron scattering, fluorescence recovery after photobleaching, coarse-grained molecular dynamics simulations provide descriptions model that formed macromolecules from nucleolar granular components (GCs). We show minimal facsimiles GCs form network fluids featuring spatial inhomogeneities across different length scales reflect contributions distinct protein peptide domains. network-like inhomogeneous is characterized coexistence liquid- gas-like macromolecular densities engenders bimodality dynamics. These insights suggest multivalent proteins share features with systems such as patchy or hairy colloids.

Language: Английский

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Single-fluorogen imaging reveals distinct environmental and structural features of biomolecular condensates

Nature Physics, Journal Year: 2025, Volume and Issue: unknown

Published: March 14, 2025

Language: Английский

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Mesoscale structure–function relationships in mitochondrial transcriptional condensates

Proceedings of the National Academy of Sciences, Journal Year: 2022, Volume and Issue: 119(41)

Published: Oct. 3, 2022

In live cells, phase separation is thought to organize macromolecules into membraneless structures known as biomolecular condensates. Here, we reconstituted transcription in condensates from purified mitochondrial components using optimized vitro reaction conditions probe the structure–function relationships of We find that core mt-transcription machinery form multiphasic, viscoelastic vitro. Strikingly, rates condensate-mediated are substantially lower than solution. The decrease transcriptional associated with formation vesicle-like driven by production and accumulation RNA during transcription. generation alters global behavior organization within Coarse-grained simulations mesoscale at equilibrium show stably assemble multiphasic vesicles formed result dynamical arrest. Overall, our findings illustrate complex transcribing, multicomponent condensates, they highlight intimate, bidirectional interplay structure function

Language: Английский

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Dynamical control enables the formation of demixed biomolecular condensates

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Nov. 24, 2023

Abstract Cellular matter can be organized into compositionally distinct biomolecular condensates. For example, in Ashbya gossypii , the RNA-binding protein Whi3 forms condensates with different RNA molecules. Using criteria derived from a physical framework for explaining how form spontaneously via thermodynamic considerations, we find that vitro mainly heterotypic interactions binary mixtures of and RNA. However, within these condensates, molecules become dynamically arrested. As result, ternary systems, simultaneous additions pairs lead to well-mixed whereas delayed addition an component results compositional distinctness. Therefore, identities achieved dynamical control, being driven, at least partially, by arrest Finally, show synchronizing production RNAs leads more well-mixed, as opposed vivo.

Language: Английский

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Developments in describing equilibrium phase transitions of multivalent associative macromolecules

Current Opinion in Structural Biology, Journal Year: 2023, Volume and Issue: 79, P. 102540 - 102540

Published: Feb. 16, 2023

Language: Английский

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