Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Shear relaxation governs fusion dynamics of biomolecular condensates.

ABSTRACT: Phase-separated biomolecular condensates must respond agilely to biochemical and environmental cues in performing their wide-ranging cellular functions, but our understanding of condensate dynamics is lagging. Ample evidence now indicates biomolecular condensates as viscoelastic fluids, where shear stress relaxes at a finite rate, not instantaneously as in viscous liquids. Yet the fusion dynamics of condensate droplets has only been modeled based on viscous liquids, with fusion time given by the viscocapillary ratio (viscosity over interfacial tension). Here we used optically trapped polystyrene beads to measure the viscous and elastic moduli and the interfacial tensions of four types of droplets. Our results challenge the viscocapillary model, and reveal that the relaxation of shear stress governs fusion dynamics. These findings likely have implications for other dynamic processes such as multiphase organization, assembly and disassembly, and aging.

SUBMITTER: Ghosh A

PROVIDER: S-EPMC8514506 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Shear relaxation governs fusion dynamics of biomolecular condensates.

Ghosh Archishman A Kota Divya D Zhou Huan-Xiang HX

Nature communications 20211013 1

Phase-separated biomolecular condensates must respond agilely to biochemical and environmental cues in performing their wide-ranging cellular functions, but our understanding of condensate dynamics is lagging. Ample evidence now indicates biomolecular condensates as viscoelastic fluids, where shear stress relaxes at a finite rate, not instantaneously as in viscous liquids. Yet the fusion dynamics of condensate droplets has only been modeled based on viscous liquids, with fusion time given by the ...[more]

PMID: 34645832

Similar Datasets

Micropolarity governs the structural organization of biomolecular condensates.

Project description:Microenvironment is critical to the function of cells and organisms. One example is provided by biomolecular condensates, whose microenvironment can be vastly different from the surrounding cellular environments to engage unique biological functions. How microenvironments of biomolecular condensates affect their structure and function remains unknown. Here, we show that the arrangements and partitioning of biomolecules are dictated by the differences between the micropolarity of each subcompartment. Sufficient difference in micropolarity results in layered structures with the exterior shell presenting a more polar microenvironment than the interior core. Accordingly, micropolarity inversion is accompanied by conversions of the layered structures. These findings demonstrated the central role of the previously overlooked microenvironment in regulating the structural organization and function of membraneless organelles.

| S-EPMC10081268 | biostudies-literature

The exchange dynamics of biomolecular condensates.

Project description:A hallmark of biomolecular condensates formed via liquid-liquid phase separation is that they dynamically exchange material with their surroundings, and this process can be crucial to condensate function. Intuitively, the rate of exchange can be limited by the flux from the dilute phase or by the mixing speed in the dense phase. Surprisingly, a recent experiment suggests that exchange can also be limited by the dynamics at the droplet interface, implying the existence of an 'interface resistance'. Here, we first derive an analytical expression for the timescale of condensate material exchange, which clearly conveys the physical factors controlling exchange dynamics. We then utilize sticker-spacer polymer models to show that interface resistance can arise when incident molecules transiently touch the interface without entering the dense phase, i.e., the molecules 'bounce' from the interface. Our work provides insight into condensate exchange dynamics, with implications for both natural and synthetic systems.

| S-EPMC11424094 | biostudies-literature

Biomolecular condensates undergo a generic shear-mediated liquid-to-solid transition.

Project description:Membrane-less organelles resulting from liquid-liquid phase separation of biopolymers into intracellular condensates control essential biological functions, including messenger RNA processing, cell signalling and embryogenesis1-4. It has recently been discovered that several such protein condensates can undergo a further irreversible phase transition, forming solid nanoscale aggregates associated with neurodegenerative disease5-7. While the irreversible gelation of protein condensates is generally related to malfunction and disease, one case where the liquid-to-solid transition of protein condensates is functional, however, is that of silk spinning8,9. The formation of silk fibrils is largely driven by shear, yet it is not known what factors control the pathological gelation of functional condensates. Here we demonstrate that four proteins and one peptide system, with no function associated with fibre formation, have a strong propensity to undergo a liquid-to-solid transition when exposed to even low levels of mechanical shear once present in their liquid-liquid phase separated form. Using microfluidics to control the application of shear, we generated fibres from single-protein condensates and characterized their structural and material properties as a function of shear stress. Our results reveal generic backbone-backbone hydrogen bonding constraints as a determining factor in governing this transition. These observations suggest that shear can play an important role in the irreversible liquid-to-solid transition of protein condensates, shed light on the role of physical factors in driving this transition in protein aggregation-related diseases and open a new route towards artificial shear responsive biomaterials.

| S-EPMC7116851 | biostudies-literature

Separation of sticker-spacer energetics governs the coalescence of metastable biomolecular condensates.

Project description:Biopolymer condensates often emerge as a multi-droplet state and never coalesce into one large droplet within the experimental timespan. This contradicts the prediction of classical polymer physics which suggests the existence of one large droplet beyond the phase transition. Previous work revealed that the sticker-spacer architecture of biopolymers may dynamically stabilize the multi-droplet state. Here, we simulate the condensate coalescence using metadynamics approach and reveal two distinct physical mechanisms underlying the fusion of droplets. Condensates made of sticker-spacer polymers readily undergo a kinetic arrest when stickers exhibit slow exchange while fast exchanging stickers at similar levels of saturation allow merger to equilibrium states. On the other hand, condensates composed of homopolymers fuse readily until they reach a threshold density. We also show that the inter-condensate exchange of chains offers a general mechanism that drives the fusion. We map the range of mechanisms of kinetic arrest from slow sticker exchange dynamics to density mediated in terms of energetic separation of stickers and spacers. Our predictions appear to be in excellent agreement with recent experiments probing dynamic nature of protein-RNA condensates.

| S-EPMC10592914 | biostudies-literature

Mesoscale properties of biomolecular condensates emerging from protein chain dynamics.

Project description:Biomolecular condensates form by phase separation of biological polymers and have important functions in the cell - functions that are inherently connected to their physical properties. A remarkable aspect of such condensates is that their viscoelastic properties can vary by orders of magnitude, but it has remained unclear how these pronounced differences are rooted in the nanoscale dynamics at the molecular level. Here we investigate a series of condensates formed by complex coacervation that span about two orders of magnitude in molecular dynamics, diffusivity, and viscosity. We find that the nanoscale chain dynamics on the nano- to microsecond timescale can be accurately related to both translational diffusion and mesoscale condensate viscosity by analytical relations from polymer physics. Atomistic simulations reveal that the observed differences in friction - a key quantity underlying these relations - are caused by differences in inter-residue contact lifetimes, leading to the vastly different dynamics among the condensates. The rapid exchange of inter-residue contacts we observe may be a general mechanism for preventing dynamic arrest in compartments densely packed with polyelectrolytes, such as the cell nucleus.

| S-EPMC11468658 | biostudies-literature

Molecular structure in biomolecular condensates.

Project description:Evidence accumulated over the past decade provides support for liquid-liquid phase separation as the mechanism underlying the formation of biomolecular condensates, which include not only 'membraneless' organelles such as nucleoli and RNA granules, but additional assemblies involved in transcription, translation and signaling. Understanding the molecular mechanisms of condensate function requires knowledge of the structures of their constituents. Current knowledge suggests that structures formed via multivalent domain-motif interactions remain largely unchanged within condensates. Two different viewpoints exist regarding structures of disordered low-complexity domains within condensates; one argues that low-complexity domains remain largely disordered in condensates and their multivalency is encoded in short motifs called 'stickers', while the other argues that the sequences form cross-β structures resembling amyloid fibrils. We review these viewpoints and highlight outstanding questions that will inform structure-function relationships for biomolecular condensates.

| S-EPMC7117980 | biostudies-literature

Biomolecular Condensates in the Nucleus.

Project description:Nuclear processes such as DNA replication, transcription, and RNA processing each depend on the concerted action of many different protein and RNA molecules. How biomolecules with shared functions find their way to specific locations has been assumed to occur largely by diffusion-mediated collisions. Recent studies have shown that many nuclear processes occur within condensates that compartmentalize and concentrate the protein and RNA molecules required for each process, typically at specific genomic loci. These condensates have common features and emergent properties that provide the cell with regulatory capabilities beyond canonical molecular regulatory mechanisms. We describe here the shared features of nuclear condensates, the components that produce locus-specific condensates, elements of specificity, and the emerging understanding of mechanisms regulating these compartments.

| S-EPMC7572565 | biostudies-literature

Structural Relaxation Processes and Collective Dynamics of Water in Biomolecular Environments.

Project description:In this simulation study, we investigate the influence of biomolecular confinement on dynamical processes in water. We compare water confined in a membrane protein nanopore at room temperature to pure liquid water at low temperatures with respect to structural relaxations, intermolecular vibrations, and the propagation of collective modes. We observe distinct potential energy landscapes experienced by water molecules in the two environments, which nevertheless result in comparable hydrogen bond lifetimes and sound propagation velocities. Hence, we show that a viscoelastic argument that links slow rearrangements of the water-hydrogen bond network to ice-like collective properties applies to both, the pure liquid and biologically confined water, irrespective of differences in the microscopic structure.

| S-EPMC6476566 | biostudies-literature

Biomolecular condensates: organizers of cellular biochemistry.

Project description:Biomolecular condensates are micron-scale compartments in eukaryotic cells that lack surrounding membranes but function to concentrate proteins and nucleic acids. These condensates are involved in diverse processes, including RNA metabolism, ribosome biogenesis, the DNA damage response and signal transduction. Recent studies have shown that liquid-liquid phase separation driven by multivalent macromolecular interactions is an important organizing principle for biomolecular condensates. With this physical framework, it is now possible to explain how the assembly, composition, physical properties and biochemical and cellular functions of these important structures are regulated.

| S-EPMC7434221 | biostudies-literature

Biomolecular condensates create phospholipid-enriched microenvironments.

Project description:Proteins and RNA can phase separate from the aqueous cellular environment to form subcellular compartments called condensates. This process results in a protein-RNA mixture that is chemically different from the surrounding aqueous phase. Here, we use mass spectrometry to characterize the metabolomes of condensates. To test this, we prepared mixtures of phase-separated proteins and extracts of cellular metabolites and identified metabolites enriched in the condensate phase. Among the most condensate-enriched metabolites were phospholipids, due primarily to the hydrophobicity of their fatty acyl moieties. We found that phospholipids can alter the number and size of phase-separated condensates and in some cases alter their morphology. Finally, we found that phospholipids partition into a diverse set of endogenous condensates as well as artificial condensates expressed in cells. Overall, these data show that many condensates are protein-RNA-lipid mixtures with chemical microenvironments that are ideally suited to facilitate phospholipid biology and signaling.

| S-EPMC10922641 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data