Protein-driven colloid-osmotic pressure controls nuclear size, organization, and function
- 1Institute of Biochemistry, Department of Biology, ETH Zurich, Zurich, Switzerland; Bringing Materials to Life Initiative, ETH Zurich, Zurich, Switzerland
Abstract
The size of the cell nucleus is tightly controlled and changes in nuclear size correlate with altered nuclear function during development, cell differentiation and senescence. How nuclear size is regulated and whether changes thereof are functionally relevant remains unclear. Here, we demonstrate that nuclear size is determined by the osmotic pressure exerted by proteins in yeast, human cells and frog egg extracts. The biophysical model we establish solves the long-standing question of how the nuclear-to-cytoplasmic ratio is regulated and maintained. Furthermore, altering protein-driven osmotic balance modulates the physical properties of the nucleus, with a direct effect on chromatin organization and gene expression: Nuclear enlargement causes the dissolution of heterochromatic structures and derepression of subtelomeres and transposons, while simultaneously down-regulating highly expressed housekeeping genes. Importantly, these global transcriptional patterns closely mimic the gene expression changes that occur as yeast, human, and drosophila cells enlarge. Importantly, artificially forcing nuclear compression is sufficient to reverse these size-associated expression changes. Together, our findings provide a quantitative, mechanistic explanation for the coupling between the size of the nucleus and the cell, and they establish nuclear size as a modulator of chromatin organization and gene expression.
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BibTeX
@misc{ohsawa2026proteindriven,
title = {{Protein-driven colloid-osmotic pressure controls nuclear size, organization, and function}},
author = {S. Ohsawa and G. A. Sancho and G. Narduzzi and W. Zhao and D. Lakhe and M. E. Estrada and A. Biswas and H. Moriizumi and E. Zatulovskiy and S. Reber and M. Jagannathan and G. E. Neurohr},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.03.749057},
url = {https://www.biorxiv.org/content/10.64898/2026.09.03.749057v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Protein-driven colloid-osmotic pressure controls nuclear size, organization, and function
AU - S. Ohsawa
AU - G. A. Sancho
AU - G. Narduzzi
AU - W. Zhao
AU - D. Lakhe
AU - M. E. Estrada
AU - A. Biswas
AU - H. Moriizumi
AU - E. Zatulovskiy
AU - S. Reber
AU - M. Jagannathan
AU - G. E. Neurohr
PY - 2026
DA - 2026/09/03
PB - bioRxiv
DO - 10.64898/2026.09.03.749057
UR - https://www.biorxiv.org/content/10.64898/2026.09.03.749057v1
AB - The size of the cell nucleus is tightly controlled and changes in nuclear size correlate with altered nuclear function during development, cell differentiation and senescence. How nuclear size is regulated and whether changes thereof are functionally relevant remains unclear. Here, we demonstrate that nuclear size is determined by the osmotic pressure exerted by proteins in yeast, human cells and frog egg extracts. The biophysical model we establish solves the long-standing question of how the nuclear-to-cytoplasmic ratio is regulated and maintained. Furthermore, altering protein-driven osmotic balance modulates the physical properties of the nucleus, with a direct effect on chromatin organization and gene expression: Nuclear enlargement causes the dissolution of heterochromatic structures and derepression of subtelomeres and transposons, while simultaneously down-regulating highly expressed housekeeping genes. Importantly, these global transcriptional patterns closely mimic the gene expression changes that occur as yeast, human, and drosophila cells enlarge. Importantly, artificially forcing nuclear compression is sufficient to reverse these size-associated expression changes. Together, our findings provide a quantitative, mechanistic explanation for the coupling between the size of the nucleus and the cell, and they establish nuclear size as a modulator of chromatin organization and gene expression.
ER -