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A framework for understanding the functions of biomolecular condensates across scales
Open accessAbstract
Biomolecular condensates are found throughout eukaryotic cells, including in the nucleus, in the cytoplasm and on membranes. They are also implicated in a wide range of cellular functions, organizing molecules that act in processes ranging from RNA metabolism to signalling to gene regulation. Early work in the field focused on identifying condensates and understanding how their physical properties and regulation arise from molecular constituents. Recent years have brought a focus on understanding condensate functions. Studies have revealed functions that span different length scales: from molecular (modulating the rates of chemical reactions) to mesoscale (organizing large structures within cells) to cellular (facilitating localization of cellular materials and homeostatic responses). In this Roadmap, we discuss representative examples of biochemical and cellular functions of biomolecular condensates from the recent literature and organize these functions into a series of non-exclusive classes across the different length scales. We conclude with a discussion of areas of current interest and challenges in the field, and thoughts about how progress may be made to further our understanding of the widespread roles of condensates in cell biology.
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“The second systems biology criterion follows from the observation that integrated function is only possible via structured spatial heterogeneity, that is, that spatial heterogeneity is crucial to cellular function.”
From ‘Whole Organism’, Systems Biology, and Top-Down Criteria for Evaluating Scenarios for the Origin of Life (2021) · cites this paper as [45]
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BackgroundАлексеенко, И. В., Kondratyeva, L. G., Чернов, И. П., & Sverdlov, E. D. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24032796 · Cited by 8
The arrested state of processing bodies supports mRNA regulation in early developmentPreprint
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Spatiotemporal solidification of α-synuclein inside the liquid dropletsPreprint
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Temperature-induced changes in protein interactions control RNA recruitment to G3BP1 condensatesPreprint
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Context-dependent Interactors Regulate TDP-43 Dysfunction in ALS/FTLDPreprint
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“Given that proteins in physiological conditions stay near their super-saturation concentrations (Vecchi et al., 2020), many can sample the three most prevalent states: native, droplet, and amyloid (Fuxreiter & Vendruscolo, 2021).”
BackgroundDroplet Differentiation by a Chemical Switch
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“Labeled scaffold proteins are often used to identify the location and type of biological condensates as foci that reveal the presence of dense assemblies of scaffold [12].”
BackgroundAlphaFold2-based prediction of the co-condensation propensity of proteins
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“Liquid-like condensates can mature as stronger intra-condensate interactions develop making them more gel-like and less spherical over time (Lyon et al, 2021; Villegas et al, 2022).”
Spontaneous Formation of Core–Shell Microdroplets during Conventional Coacervate Phase Separation
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“We note that the droplet state is often the physiological form of proteins that are important for functions, such as the regulation of the rates of chemical reactions or gene expression, and the coordination of repair or homeostatic machineries (Lyon et al., 2021).”
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“(5) in stationary state in a system with angular symmetry using the boundary conditions φin(R) = φ eq in and ∂rφin(0) = 0 .”
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Composition can buffer protein dynamics within liquid-like condensates
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Metadata
- Authors
- Lyon, A. S., Peeples, W. B., & Rosen, M. K.
- Affiliations
- Howard Hughes Medical Institute (US)
- Corresponding author
- Rosen, Michael K.
- Venue
- Nature Reviews Molecular Cell Biology
- Published
- 2020-11-09
- Volume
- 22
- Issue
- 3
- Pages
- 215-235
- ISSN
- 1471-0072 (ISSN-L)
- 1471-0080
- PMC
- PMC8574987
- OpenAlex
- W3099323319
- Cited by
- 895
- References
- 233
- Citations by year
- 2026: 149 · 2025: 186 · 2024: 175 · 2023: 172 · 2022: 115 · 2021: 95 · 2020: 2
- FWCI
- 9.35
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Nature Reviews Molecular Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institute of General Medical Sciences (F32GM136058)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- biomolecular condensates, liquid-liquid phase separation, length scales, RNA metabolism, gene expression regulation, cell organization, signal transduction, reaction rate, cellular homeostasis
- MeSH terms
- Animals, Biochemical Phenomena, Cell Physiological Phenomena, Cytoplasm, Eukaryotic Cells, Humans, Organelles, Macromolecular Substances, Multiprotein Complexes, Protein Aggregates
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