Conserved nucleocytoplasmic density homeostasis drives cellular organization across eukaryotes

Biswas A, Muñoz O, Kim K, Hoege C, Lorton BM, Nikolay R, Kraushar ML, Shechter D, Guck J, Zaburdaev V, Reber S (2025)

Publication Type: Journal article

Publication year: 2025

Journal

Nature Communications Nature Publishing Group: Nature Communications

Book Volume: 16

Article Number: 7597

Journal Issue: 1

DOI: 10.1038/s41467-025-62605-0

Abstract

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 with CRIS profile

Jochen Guck
Vasily Zaburdaev

Involved external institutions

Max-Planck-Institut für Infektionsbiologie / Max Planck Institute for Infection Biology DE Germany (DE) Max-Planck-Institut für die Physik des Lichts (MPL) / Max Planck Institute for the Science of Light DE Germany (DE) Max-Planck-Institut für molekulare Zellbiologie und Genetik / Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG) DE Germany (DE) Max-Planck-Institut für molekulare Genetik / Max Planck Institute for Molecular Genetics DE Germany (DE) Cardiovascular Research Foundation US United States (USA) (US)

How to cite

APA:

Biswas, A., Muñoz, O., Kim, K., Hoege, C., Lorton, B.M., Nikolay, R.,... Reber, S. (2025). Conserved nucleocytoplasmic density homeostasis drives cellular organization across eukaryotes. Nature Communications, 16(1). https://doi.org/10.1038/s41467-025-62605-0

MLA:

Biswas, Abin, et al. "Conserved nucleocytoplasmic density homeostasis drives cellular organization across eukaryotes." Nature Communications 16.1 (2025).

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