Enzymes can activate and mobilize dense biomolecular condensates across scales
14 affiliations
- 1Protein Engineering and Evolution Unit, Okinawa Institute of Science and Technology Graduate University, Onna, Japan
- 2Section of Physiology and Biochemistry, Department of Medicine and Surgery, University of Perugia, Perugia, Italy
- 3Max Planck Institute for Dynamics and Self-Organization (MPI-DS), Göttingen, Germany
- 4Theoretical Molecular Science Laboratory, RIKEN Cluster for Pioneering Research, Saitama, Japan
- 5Wenzhou Key Laboratory of Biophysics, Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, China
- 6DAMTP, Centre for Mathematical Sciences, University of Cambridge, Cambridge, UK
- 7Department of Chemistry, Institute of Pure and Applied Sciences, University of Tsukuba, Tsukuba, Japan
- 8Computational Biophysics Research Team, RIKEN Center for Computational Science, Kobe, Japan. [email protected]
- 9Department of Physics, Graduate School of Science, The University of Tokyo, Tokyo, Japan. [email protected]
- 10Theoretical Molecular Science Laboratory, RIKEN Cluster for Pioneering Research, Saitama, Japan. [email protected]
- 11Max Planck Institute for Dynamics and Self-Organization (MPI-DS), Göttingen, Germany. [email protected]
- 12Rudolf Peierls Centre for Theoretical Physics, University of Oxford, Oxford, UK. [email protected]
- 13Institute for Protein Research, Osaka University, Suita, Japan. [email protected]
- 14Protein Engineering and Evolution Unit, Okinawa Institute of Science and Technology Graduate University, Onna, Japan. [email protected]
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.
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BibTeX
@article{dindo2026enzymes,
title = {{Enzymes can activate and mobilize dense biomolecular condensates across scales}},
author = {Mirco Dindo and Jakob Metson and Weitong Ren and Michalis Chatzittofi and Kiyoshi Yagi and Alessandro Bevilacqua and Erika Fukuhara and Yuji Sugita and Ramin Golestanian and Paola Laurino},
journal = {Nature Communications},
year = {2026},
month = oct,
doi = {10.1038/s41467-026-77666-y},
url = {https://www.nature.com/articles/s41467-026-77666-y},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Enzymes can activate and mobilize dense biomolecular condensates across scales
AU - Mirco Dindo
AU - Jakob Metson
AU - Weitong Ren
AU - Michalis Chatzittofi
AU - Kiyoshi Yagi
AU - Alessandro Bevilacqua
AU - Erika Fukuhara
AU - Yuji Sugita
AU - Ramin Golestanian
AU - Paola Laurino
PY - 2026
DA - 2026/10/30
JO - Nature Communications
DO - 10.1038/s41467-026-77666-y
UR - https://www.nature.com/articles/s41467-026-77666-y
AB - 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.
SN - 2041-1723
ER -