The correlation between cell and nucleus size is explained by an eukaryotic cell growth model
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Abstract
In eukaryotes, the cell volume is observed to be strongly correlated with the nuclear volume. The slope of this correlation depends on the cell type, growth condition, and the physical environment of the cell. We develop a computational model of cell growth and proteome increase, incorporating the kinetics of amino acid import, protein/ribosome synthesis and degradation, and active transport of proteins between the cytoplasm and the nucleoplasm. We also include a simple model of ribosome biogenesis and assembly. Results show that the cell volume is tightly correlated with the nuclear volume, and the cytoplasm-nucleoplasm transport rates strongly influence the cell growth rate as well as the cell/nucleus volume ratio (C/N ratio). Ribosome assembly and the ratio of ribosomal proteins to mature ribosomes also influence the cell volume and the cell growth rate. We find that in order to regulate the cell growth rate and the cell/nucleus volume ratio, the cell must optimally control groups of kinetic and transport parameters together, which could explain the quantitative roles of canonical growth pathways. Finally, although not explicitly demonstrated in this work, we point out that it is possible to construct a detailed proteome distribution using our model and RNAseq data, provided that a quantitative cell division mechanism is known.
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Cites
Single-cell RNA-seq: advances and future challenges
Saliba, A.-E., Westermann, A. J., Gorski, S. A., & Vogel, J. (2014) · Nucleic Acids Research · doi:10.1093/nar/gku555 · Cited by 847 · see citing works
Milo, R. (2013) · BioEssays · doi:10.1002/bies.201300066 · Cited by 643 · cited 4× · see citing works
“Symbol Description Yeast Values Mammalian Values Source AC Cytoplasmic amino acid (AA) number 3200× 10(6) 21600× 10(6) [16, 29,50,51] PC Cytoplasmic non-ribosomal protein number 15× 10(6) 660× 10(6) [25, 30,31,52] RC Cytoplasmic mature ribosome number 0.”
BackgroundInfluentialFunctional Metabolomics Describes the Yeast Biosynthetic Regulome
Mülleder, M., Calvani, E., Alam, M. T., Wang, R. K., Eckerstorfer, F., Zelezniak, A., & Ralser, M. (2016) · Cell · doi:10.1016/j.cell.2016.09.007 · Cited by 178 · see citing works
Ribosome biogenesis in replicating cells: integration of experiment and theory
Earnest, E. E., Cole, J. A., Peterson, J. R., Hallock, M. J., Kuhlman, T. E., & Luthey‐Schulten, Z. (2016) · Biopolymers · doi:10.1002/bip.22892 · Cited by 16 · see citing works
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- Authors
- Wu, Y., Pegoraro, A. F., Weitz, D. A., Janmey, P., & Sun, S. X.
- Affiliations
- Johns Hopkins University (US)
- University of Ottawa (CA)
- Harvard University (US)
- University of Pennsylvania (US)
- Corresponding author
- Sun, Sean X.
- Venue
- PLOS Computational Biology
- Publisher
- Public Library of Science (PLoS)
- Published
- 2022-02-18
- Volume
- 18
- Issue
- 2
- Pages
- e1009400
- ISSN
- 1553-734X (ISSN-L)
- 1553-7358
- PMC
- PMC8893647
- OpenAlex
- W4220917510
- Cited by
- 72
- References
- 4
- Citations by year
- 2026: 14 · 2025: 12 · 2024: 21 · 2023: 18 · 2022: 7
- FWCI
- 4.74
- Type
- journal article
- Language
- en
- Update notices
- new_version (2022-03-03)
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS Computational Biology (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institute of General Medical Sciences (R01GM134542, R35GM136259)
- NIH (P01HL120839)
- Directorate for Engineering (DMR-1420570)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Molecular Research
- Keywords
- cell size, nuclear size, cell growth model, cell volume, nuclear volume, ribosome biogenesis, ribosome assembly, ribosomal proteins, protein synthesis, protein degradation, cell growth rate
- MeSH terms
- Cell Nucleus, Eukaryotic Cells, Ribosomal Proteins, Ribosomes, RNA, Ribosomal, Proteome, Active Transport, Cell Nucleus
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