Material properties of biomolecular condensates emerge from nanoscale dynamics

Biomolecular condensates form by phase separation of biological polymers and have important functions in the cell-functions that are inherently linked to their physical properties at different scales. A notable aspect of such membraneless organelles is that their viscoelastic properties can vary by orders of magnitude, but it has remained unclear how these pronounced differences are rooted in the nanoscale dynamics at the molecular level. Here, we investigate a series of condensates formed by complex coacervation of highly charged disordered proteins and polypeptides that span about two orders of magnitude in bulk viscosity. We find that their viscosity is highly correlated with protein translational diffusion and nano- to microsecond chain dynamics. Remarkably, analytical relations from polymer physics can predict condensate viscosity from diffusivity and chain dynamics, and vice versa, even for more hydrophobic disordered proteins and for synthetic polyelectrolytes, indicating a mechanistic link across several decades of length- and timescales. Atomistic simulations reveal that the observed differences in friction-a key quantity underlying these relations-reflect differences in interresidue contact lifetimes as a function of arginine content and salt concentration, leading to the vastly different dynamics among condensates. The rapid exchange of interresidue contacts we observe may be a general mechanism for preventing dynamic arrest in compartments densely packed with polyelectrolytes, such as the cell nucleus.

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Publication Details

Journal
Proceedings of the National Academy of Sciences
Published
2025-06-02
DOI
https://doi.org/10.1073/pnas.2424135122
Citations
39
Primary Topic
RNA Research and Splicing
Type
article
Field-Weighted Citation Impact
30.63

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article

Material properties of biomolecular condensates emerge from nanoscale dynamics

Andrea Sottini, Daniel Nettels, Benjamin Schuler, Robert B. Best et al.
39 citations
Proceedings of the National Academy of Sciences
RNA Research and Splicing
30.63
article

Material properties of biomolecular condensates emerge from nanoscale dynamics

Andrea Sottini, Daniel Nettels, Benjamin Schuler, Robert B. Best, Aritra Chowdhury, Miloš T. Ivanović, Nicola Galvanetto, Simone Grosso
article en
39 citations

Abstract

Biomolecular condensates form by phase separation of biological polymers and have important functions in the cell-functions that are inherently linked to their physical properties at different scales. A notable aspect of such membraneless organelles is that their viscoelastic properties can vary by orders of magnitude, but it has remained unclear how these pronounced differences are rooted in the nanoscale dynamics at the molecular level. Here, we investigate a series of condensates formed by complex coacervation of highly charged disordered proteins and polypeptides that span about two orders of magnitude in bulk viscosity. We find that their viscosity is highly correlated with protein translational diffusion and nano- to microsecond chain dynamics. Remarkably, analytical relations from polymer physics can predict condensate viscosity from diffusivity and chain dynamics, and vice versa, even for more hydrophobic disordered proteins and for synthetic polyelectrolytes, indicating a mechanistic link across several decades of length- and timescales. Atomistic simulations reveal that the observed differences in friction-a key quantity underlying these relations-reflect differences in interresidue contact lifetimes as a function of arginine content and salt concentration, leading to the vastly different dynamics among condensates. The rapid exchange of interresidue contacts we observe may be a general mechanism for preventing dynamic arrest in compartments densely packed with polyelectrolytes, such as the cell nucleus.

Proceedings of the National Academy of SciencesVol. 122(23)
National Institutes of Health (US), University of Zurich (CH), National Institute of Diabetes and Digestive and Kidney Diseases (US)
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, Novo Nordisk Fonden, National Institute of Diabetes and Digestive and Kidney Diseases, HORIZON EUROPE Marie Sklodowska-Curie Actions
Openalex Percentile: Top 0%
RNA Research and Splicing
30.63
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