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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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VUS next in rare diseases? Deciphering genetic determinants of biomolecular condensation
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“BCs have thus emerged as primary organizers at different scales, and their role in both physiological and pathological processes has been fully demonstrated [32, 33, 60, 65–67].”
BackgroundYkuR functions as a protein deacetylase in Streptococcus mutans
Ma, Q., Li, J., Yu, S., Zhou, J., Liu, Y., Wang, X., Ye, D., Wu, Y., Gong, T., Zhang, Q., et al. (2024) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2407820121 · Cited by 4
“Biological functions are accomplished by interactions and chemical reactions among biomolecules ( 30 ).”
Beyond equilibrium: roles of RNAs in condensate control
Muzzopappa, F., & Erdel, F. (2025) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2024.102304 · Cited by 4
Targeting viruses in their phase
Strzyz, P. J. (2021) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-021-00400-7 · Cited by 4
Monzón, A. M., Piovesan, D., & Fuxreiter, M. (2022) · Biomolecules · doi:10.3390/biom12010092 · Cited by 4
“Discussion and Conclusions Biomolecular condensates formed by liquid–liquid phase separation are associated with a wide-range of biological activities [2].”
BackgroundStochastic dynamics of single molecules across phase boundariesPreprint
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Clustering within a single-component biomolecular condensatePreprint
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Transport kinetics across interfaces between coexisting liquid phasesPreprint
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Raman Dissection of Water-Interaction Coupling in Condensate-Relevant Peptides
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Dynamic Structural Organization of Biomolecular Condensates in Escherichia coli Cells
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Protein codes and mobility together shape cellular function and disease
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Cajal’s organization of neuronal nucleus revisited
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“Liquid – liquid phase separation (LLPS) has emerged as a unifying framework for understanding how cells organize biochemical reactions without membrane-bound compartments (Lyon et al., 2021).”
Advances in the construction and biological applications of DNA condensates
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Machine Learning‐Guided Engineering of Protein Phase Separation Properties in Immune Regulation
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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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