{ "abstract": "Biomolecular condensates have so far been studied in terms of their structural, compositional, and functional properties. However, condensate enzymatic activity - a key aspect of cellular metabolism - remains unexplored due to the complexity of the system. In this study, using a combination of experimental, computational and theoretical techniques, we have discovered that the non-equilibrium activity which originates from catalytic reactions couples with the environment through various feedback mechanisms across five orders of magnitude of length scales. We observe that condensed enzymes catalyze more rapidly in the presence of crowding proteins and show that the increased enzymatic activity within these droplets stems from the emergence of lower-energy protein conformations induced by the highly crowded environment. Despite the crowding in the environment of the droplet, which might suggest an effective increase in its overall viscosity, we find that it becomes more agile, as evidenced by the observation of enhanced diffusion and macroscopic flow, due to the enzymatic activity. These findings shed light on the dynamic interplay between enzymatic activity, composition and crowding in condensates, and their roles on the mobility and accessibility of various functional units in these environments, expanding our understanding of liquid-liquid phase separation in metabolically active conditions.", "abstract_shown": true, "affiliations": [ "Protein Engineering and Evolution Unit, Okinawa Institute of Science and Technology Graduate University, Onna, Japan", "Section of Physiology and Biochemistry, Department of Medicine and Surgery, University of Perugia, Perugia, Italy", "Max Planck Institute for Dynamics and Self-Organization (MPI-DS), Göttingen, Germany", "Theoretical Molecular Science Laboratory, RIKEN Cluster for Pioneering Research, Saitama, Japan", "Wenzhou Key Laboratory of Biophysics, Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, China", "DAMTP, Centre for Mathematical Sciences, University of Cambridge, Cambridge, UK", "Department of Chemistry, Institute of Pure and Applied Sciences, University of Tsukuba, Tsukuba, Japan", "Computational Biophysics Research Team, RIKEN Center for Computational Science, Kobe, Japan. sugita@riken.jp", "Department of Physics, Graduate School of Science, The University of Tokyo, Tokyo, Japan. sugita@riken.jp", "Theoretical Molecular Science Laboratory, RIKEN Cluster for Pioneering Research, Saitama, Japan. sugita@riken.jp", "Max Planck Institute for Dynamics and Self-Organization (MPI-DS), Göttingen, Germany. ramin.golestanian@ds.mpg.de", "Rudolf Peierls Centre for Theoretical Physics, University of Oxford, Oxford, UK. ramin.golestanian@ds.mpg.de", "Institute for Protein Research, Osaka University, Suita, Japan. paola.laurino@oist.jp", "Protein Engineering and Evolution Unit, Okinawa Institute of Science and Technology Graduate University, Onna, Japan. paola.laurino@oist.jp" ], "article_type": "research article", "arxiv": null, "author_total": 10, "authors": [ { "affs": [ 0, 1 ], "name": "Mirco Dindo", "orcid": "0000-0001-6455-3200" }, { "affs": [ 2 ], "name": "Jakob Metson", "orcid": "0009-0004-5966-6074" }, { "affs": [ 3, 4 ], "name": "Weitong Ren", "orcid": "0000-0001-8889-4587" }, { "affs": [ 5, 2 ], "name": "Michalis Chatzittofi", "orcid": "0009-0007-3898-3638" }, { "affs": [ 6, 3 ], "name": "Kiyoshi Yagi", "orcid": "0000-0003-1120-9355" }, { "affs": [ 0 ], "name": "Alessandro Bevilacqua", "orcid": "0000-0002-8541-8603" }, { "affs": [ 0 ], "name": "Erika Fukuhara", "orcid": "0009-0006-7724-8698" }, { "affs": [ 7, 8, 9 ], "name": "Yuji Sugita", "orcid": "0000-0001-9738-9216" }, { "affs": [ 10, 11 ], "name": "Ramin Golestanian", "orcid": "0000-0002-3149-4002" }, { "affs": [ 12, 13 ], "name": "Paola Laurino", "orcid": "0000-0002-3725-2645" } ], "bibtex": "https://research.draconitic.com/paper/a66hkcs32jsda.bib", "cited_by": 8, "doi": "10.1038/s41467-026-77666-y", "fulltext_url": "https://europepmc.org/articles/PMC13722700", "id": "a66hkcs32jsda", "issns": [ "2041-1723" ], "landing_url": "https://www.nature.com/articles/s41467-026-77666-y", "language": "eng", "licence": "CC-BY-NC-ND-4.0", "licence_label": "CC BY-NC-ND 4.0", "licence_source": "article", "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0", "metadata_licence": null, "native_subjects": [ [ "heading", "Article" ], [ "openalex", "1312|RNA Research and Splicing" ] ], "openalex": "W4406926255", "pdf_url": "https://www.nature.com/articles/s41467-026-77666-y.pdf", "pmcid": "PMC13722700", "pmid": "42963352", "published": "2026-10-30", "publisher": "Springer Science and Business Media LLC", "ris": "https://research.draconitic.com/paper/a66hkcs32jsda.ris", "sources": [ { "first_seen": "2026-10-30T12:17:39Z", "native_id": "10.1038/s41467-026-77666-y", "source": "crossref", "url": "https://www.nature.com/articles/s41467-026-77666-y" }, { "first_seen": "2026-11-02T03:21:21Z", "native_id": "MED:42963352", "source": "europepmc", "url": "https://europepmc.org/article/MED/42963352" }, { "first_seen": "2026-11-02T13:20:38Z", "native_id": "W4406926255", "source": "openalex", "url": "https://doi.org/10.1038/s41467-026-77666-y" }, { "first_seen": "2026-11-04T12:21:28Z", "native_id": "PMC13722700", "source": "pmc", "url": "https://doi.org/10.1038/s41467-026-77666-y" } ], "subjects": [ { "field": "biochemistry", "origin": "openalex:1312|RNA Research and Splicing", "subfield": "molecular-biology" } ], "title": "Enzymes can activate and mobilize dense biomolecular condensates across scales", "title_text": "Enzymes can activate and mobilize dense biomolecular condensates across scales", "type": "peer-reviewed", "updated_at": "2026-11-04T13:21:07Z", "url": "https://research.draconitic.com/paper/a66hkcs32jsda", "venue": "Nature Communications", "versions": [] }