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PreprintCited by 31Nuclear Structure and FunctionProtein Structure and DynamicsGenomics and Chromatin Dynamics

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Conserved nucleocytoplasmic density homeostasis drives cellular organization across eukaryotes

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Biswas, Abin, Muñoz, Omar, Kim, Kyoohyun, Hoege, Carsten, Lorton, Benjamin M., Shechter, David, Guck, Jochen, Zaburdaev, Vasily, Reber, Simone·2023·Nature Communications
DOI 10.1101/2023.09.05.556409PMC PMC12356907

Preprint — published as 10.1038/s41467-025-62605-0

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Abstract

The packing and confinement of macromolecules in the cytoplasm and nucleoplasm has profound implications for cellular biochemistry. How intracellular density distributions vary and affect cellular physiology remains largely unknown. Here, we show that the nucleus is less dense than the cytoplasm and that living systems establish and maintain a constant density ratio between these compartments. Using label-free biophotonics and theory, we show that nuclear density is set by a pressure balance across the nuclear envelope in vitro , in vivo and during early development. Nuclear transport establishes a specific nuclear proteome that exerts a colloid osmotic pressure, which, assisted by entropic chromatin pressure, draws water into the nucleus. Using C. elegans , we show that while nuclear-to-cytoplasmic (N/C) volume ratios change during early development, the N/C density ratio is robustly maintained. We propose that the maintenance of a constant N/C density ratio is the biophysical driver of one of the oldest tenets of cell biology: the N/C volume ratio. In summary, this study reveals a previously unidentified homeostatic coupling of macromolecular densities that drives cellular organization with implications for pathophysiologies such as senescence and cancer.

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Metadata

Authors
Biswas, A., Muñoz, O., Kim, K., Hoege, C., Lorton, B. M., Shechter, D., Guck, J., Zaburdaev, V., & Reber, S.
Affiliations
  • Max Planck Institute for Infection Biology (DE)
  • Friedrich-Alexander-Universität Erlangen-Nürnberg (DE)
  • Max Planck Institute for the Science of Light (DE)
  • Max Planck Institute of Molecular Cell Biology and Genetics (DE)
  • Albert Einstein College of Medicine (US)
  • Berliner Hochschule für Technik (DE)
Corresponding author
  • Guck, Jochen
  • Zaburdaev, Vasily
  • Reber, Simone
ORCID
Venue
Nature Communications
Publisher
openRxiv
Published
2023-09-06
Volume
16
Issue
1
Pages
7597-7597
ISSN
2041-1723 (ISSN-L)
DOI
10.1101/2023.09.05.556409
PMC
PMC12356907
OpenAlex
W4413257272
Cited by
31
References
1
Citations by year
2026: 12 · 2025: 12 · 2024: 5 · 2023: 2
FWCI
7.21
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Nature Communications (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • OPUS FAU (Kooperativer Bibliotheksverbund Berlin-Brandenburg (KOBV), on behalf of the Universitätsbibliothek Erlangen-Nürnberg) (submittedVersion, cc-by)
  • MPG.PuRe (Max Planck Society) (submittedVersion, cc-by)
Funders
  • European Molecular Biology Laboratory
  • Deutsche Forschungsgemeinschaft (RE 3925/1‐1, 528483508, SPP2191)
  • Eidgenössische Technische Hochschule Zürich
  • Max-Planck-Gesellschaft
  • RWTH Aachen University
  • Freie Universität Berlin
  • National Institutes of Health
  • National Institute of General Medical Sciences (R01GM108646, R01GM135614)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Keywords
macromolecular crowding, nuclear volume, nuclear proteome, nuclear transport, cellular senescence, Caenorhabditis elegans development
MeSH terms
Animals, Cell Nucleus, Cytoplasm, Homeostasis, Nuclear Envelope, Osmotic Pressure, Caenorhabditis elegans, Active Transport, Cell Nucleus, Caenorhabditis elegans Proteins

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