Conserved nucleocytoplasmic density homeostasis drives cellular organization across eukaryotes
The confinement of macromolecules has profound implications for cellular biochemistry. It generates environments with specific physical properties affecting diffusion, macromolecular crowding, and reaction rates. Yet, it remains unknown how intracellular density distributions emerge and affect cellular physiology. Here, we show that the nucleus is less dense than the cytoplasm and that living systems establish a conserved density ratio between these compartments due to a pressure balance across the nuclear envelope. Nuclear transport establishes a specific nuclear proteome that exerts a colloid osmotic pressure, which, assisted by chromatin pressure, increases nuclear volume. During C. elegans development, the nuclear-to-cytoplasmic density ratio is robustly maintained even when nuclear-to-cytoplasmic volume ratios change. We show that loss of density homeostasis correlates with altered cell functions like senescence and propose density distributions as key markers in pathophysiology. In summary, this study reveals a homeostatic coupling of macromolecular densities that drives cellular organization and function.
Authors
- Matthew L. Kraushar (ORCID: https://orcid.org/0000-0002-7359-0318)
- Rainer Nikolay (ORCID: https://orcid.org/0000-0003-4713-2548)
- Kyoohyun Kim (ORCID: https://orcid.org/0000-0003-1808-775X)
- Jochen Guck (ORCID: https://orcid.org/0000-0002-1453-6119)
- Vasily Zaburdaev (ORCID: https://orcid.org/0000-0001-8234-3442)
- David Shechter (ORCID: https://orcid.org/0000-0001-9388-6004)
- Carsten Hoege
- Benjamin M. Lorton (ORCID: https://orcid.org/0000-0002-8553-2078)
- Abin Biswas (ORCID: https://orcid.org/0000-0002-0129-8561)
- Simone Reber (ORCID: https://orcid.org/0000-0002-5287-2332)
- Omar Muñoz
Institutions
- Albert Einstein College of Medicine (US)
- Friedrich-Alexander-Universität Erlangen-Nürnberg (DE)
- WZB Berlin Social Science Center (DE)
- Max Planck Institute for Infection Biology (DE)
- Max Planck Institute for the Science of Light (DE)
- Max Planck Institute for Molecular Genetics (DE)
- Max Planck Institute for the History of Science (DE)
- Max Planck Institute of Molecular Cell Biology and Genetics (DE)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-08-15
- DOI
- https://doi.org/10.1038/s41467-025-62605-0
- Citations
- 9
- Primary Topic
- Microtubule and mitosis dynamics
- Type
- article
- Field-Weighted Citation Impact
- 10.36
Funders
- European Molecular Biology Laboratory
- Deutsche Forschungsgemeinschaft
- Eidgenössische Technische Hochschule Zürich
- Max-Planck-Gesellschaft
- RWTH Aachen University
- Freie Universität Berlin
- National Institutes of Health