Quantifying collective interactions in biomolecular phase separation
Abstract Biomolecular phase separation is an emerging theme for protein assembly and cellular organisation. The collective forces driving such condensation, however, remain challenging to characterise. Here we show that tracking the dilute phase concentration of only one component suffices to quanti...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-08-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-62437-y |
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| author | Hannes Ausserwöger Ella de Csilléry Daoyuan Qian Georg Krainer Timothy J. Welsh Tomas Sneideris Titus M. Franzmann Seema Qamar Nadia A. Erkamp Jonathon Nixon-Abell Mrityunjoy Kar Peter St George-Hyslop Anthony A. Hyman Simon Alberti Rohit V. Pappu Tuomas P. J. Knowles |
| author_facet | Hannes Ausserwöger Ella de Csilléry Daoyuan Qian Georg Krainer Timothy J. Welsh Tomas Sneideris Titus M. Franzmann Seema Qamar Nadia A. Erkamp Jonathon Nixon-Abell Mrityunjoy Kar Peter St George-Hyslop Anthony A. Hyman Simon Alberti Rohit V. Pappu Tuomas P. J. Knowles |
| author_sort | Hannes Ausserwöger |
| collection | DOAJ |
| description | Abstract Biomolecular phase separation is an emerging theme for protein assembly and cellular organisation. The collective forces driving such condensation, however, remain challenging to characterise. Here we show that tracking the dilute phase concentration of only one component suffices to quantify composition and energetics of multicomponent condensates. Applying this assay to several disease- and stress-related proteins, we find that monovalent ions can either deplete from or enrich within the dense phase in a context-dependent manner. By analysing the effect of the widely used modulator 1,6-hexanediol, we find that the compound inhibits phase separation by acting as a solvation agent that expands polypeptide chains. Extending the strategy to in cellulo data, we even quantify the relative energetic contributions of individual proteins within complex condensates. Together, our approach provides a generic and broadly applicable tool for dissecting the forces governing biomolecular condensation and guiding the rational modulation of condensate behaviour. |
| format | Article |
| id | doaj-art-ce99288b6a844e3c91b069da81472e2f |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-ce99288b6a844e3c91b069da81472e2f2025-08-24T11:36:40ZengNature PortfolioNature Communications2041-17232025-08-0116111310.1038/s41467-025-62437-yQuantifying collective interactions in biomolecular phase separationHannes Ausserwöger0Ella de Csilléry1Daoyuan Qian2Georg Krainer3Timothy J. Welsh4Tomas Sneideris5Titus M. Franzmann6Seema Qamar7Nadia A. Erkamp8Jonathon Nixon-Abell9Mrityunjoy Kar10Peter St George-Hyslop11Anthony A. Hyman12Simon Alberti13Rohit V. Pappu14Tuomas P. J. Knowles15Centre for Misfolding Diseases, Yusuf Hamied Department of Chemistry, University of CambridgeCentre for Misfolding Diseases, Yusuf Hamied Department of Chemistry, University of CambridgeCentre for Misfolding Diseases, Yusuf Hamied Department of Chemistry, University of CambridgeInstitute of Molecular Biosciences (IMB), University of GrazCentre for Misfolding Diseases, Yusuf Hamied Department of Chemistry, University of CambridgeCentre for Misfolding Diseases, Yusuf Hamied Department of Chemistry, University of CambridgeBiotechnology Center (BIOTEC), Center for Molecular and Cellular Bioengineering (CMCB), Technische Universität DresdenCambridge Institute for Medical Research, Department of Clinical Neurosciences, Clinical School, University of CambridgeCentre for Misfolding Diseases, Yusuf Hamied Department of Chemistry, University of CambridgeCambridge Institute for Medical Research, Department of Clinical Neurosciences, Clinical School, University of CambridgeMax Planck Institute of Cell Biology and Genetics (MPI-CBG)Department of Medicine (Division of Neurology), Temerty Faculty of Medicine, University Health Network, University of TorontoMax Planck Institute of Cell Biology and Genetics (MPI-CBG)Biotechnology Center (BIOTEC), Center for Molecular and Cellular Bioengineering (CMCB), Technische Universität DresdenDepartment of Biomedical Engineering and Center for Biomolecular Condensates, Washington University in St. LouisCentre for Misfolding Diseases, Yusuf Hamied Department of Chemistry, University of CambridgeAbstract Biomolecular phase separation is an emerging theme for protein assembly and cellular organisation. The collective forces driving such condensation, however, remain challenging to characterise. Here we show that tracking the dilute phase concentration of only one component suffices to quantify composition and energetics of multicomponent condensates. Applying this assay to several disease- and stress-related proteins, we find that monovalent ions can either deplete from or enrich within the dense phase in a context-dependent manner. By analysing the effect of the widely used modulator 1,6-hexanediol, we find that the compound inhibits phase separation by acting as a solvation agent that expands polypeptide chains. Extending the strategy to in cellulo data, we even quantify the relative energetic contributions of individual proteins within complex condensates. Together, our approach provides a generic and broadly applicable tool for dissecting the forces governing biomolecular condensation and guiding the rational modulation of condensate behaviour.https://doi.org/10.1038/s41467-025-62437-y |
| spellingShingle | Hannes Ausserwöger Ella de Csilléry Daoyuan Qian Georg Krainer Timothy J. Welsh Tomas Sneideris Titus M. Franzmann Seema Qamar Nadia A. Erkamp Jonathon Nixon-Abell Mrityunjoy Kar Peter St George-Hyslop Anthony A. Hyman Simon Alberti Rohit V. Pappu Tuomas P. J. Knowles Quantifying collective interactions in biomolecular phase separation Nature Communications |
| title | Quantifying collective interactions in biomolecular phase separation |
| title_full | Quantifying collective interactions in biomolecular phase separation |
| title_fullStr | Quantifying collective interactions in biomolecular phase separation |
| title_full_unstemmed | Quantifying collective interactions in biomolecular phase separation |
| title_short | Quantifying collective interactions in biomolecular phase separation |
| title_sort | quantifying collective interactions in biomolecular phase separation |
| url | https://doi.org/10.1038/s41467-025-62437-y |
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