Control of nuclear size by osmotic forces in Schizosaccharomyces pombe

  1. Joël Lemière
  2. Paula Real-Calderon
  3. Liam J Holt
  4. Thomas G Fai  Is a corresponding author
  5. Fred Chang  Is a corresponding author
  1. University of California, San Francisco, United States
  2. New York University Langone Medical Center, United States
  3. Brandeis University, United States

Abstract

The size of the nucleus scales robustly with cell size so that the nuclear-to-cell volume ratio (N/C ratio) is maintained during cell growth in many cell types. The mechanism responsible for this scaling remains mysterious. Previous studies have established that the N/C ratio is not determined by DNA amount but is instead influenced by factors such as nuclear envelope mechanics and nuclear transport. Here, we developed a quantitative model for nuclear size control based upon colloid osmotic pressure and tested key predictions in the fission yeast Schizosaccharomyces pombe. This model posits that the N/C ratio is determined by the numbers of macromolecules in the nucleoplasm and cytoplasm. Osmotic shift experiments showed that the fission yeast nucleus behaves as an ideal osmometer whose volume is primarily dictated by osmotic forces. Inhibition of nuclear export caused accumulation of macromolecules and an increase in crowding in the nucleoplasm, leading to nuclear swelling. We further demonstrated that the N/C ratio is maintained by a homeostasis mechanism based upon synthesis of macromolecules during growth. These studies demonstrate the functions of colloid osmotic pressure in intracellular organization and size control.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting file. A source data file has been provided for Figures 2-7 and Supplementary Figures.

Article and author information

Author details

  1. Joël Lemière

    University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9017-1959
  2. Paula Real-Calderon

    University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Liam J Holt

    Institute for Systems Genetics, New York University Langone Medical Center, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Thomas G Fai

    Department of Mathematics, Brandeis University, Waltham, United States
    For correspondence
    tfai@brandeis.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0383-5217
  5. Fred Chang

    University of California, San Francisco, San Francisco, United States
    For correspondence
    fred.chang@ucsf.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8907-3286

Funding

National Institutes of Health (R01 GM056836)

  • Fred Chang

National Institutes of Health (R35 GM141796)

  • Fred Chang

National Science Foundation (MCB-1638195)

  • Fred Chang

National Science Foundation (DMS-1913093)

  • Thomas G Fai

American Cancer Society

  • Liam J Holt

Pershing Square Sohn Cancer Research Alliance

  • Liam J Holt

National Institutes of Health (R01 GM132447)

  • Liam J Holt

National Institutes of Health (R37 CA240765)

  • Liam J Holt

Chan Zuckerberg Initiative

  • Liam J Holt

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

© 2022, Lemière et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 3,272
    views
  • 645
    downloads
  • 34
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Joël Lemière
  2. Paula Real-Calderon
  3. Liam J Holt
  4. Thomas G Fai
  5. Fred Chang
(2022)
Control of nuclear size by osmotic forces in Schizosaccharomyces pombe
eLife 11:e76075.
https://doi.org/10.7554/eLife.76075

Share this article

https://doi.org/10.7554/eLife.76075

Further reading

    1. Physics of Living Systems
    Jonathan H Booth, Andrew T Meek ... Malte C Gather
    Research Article

    During locomotion, soft-bodied terrestrial animals solve complex control problems at substrate interfaces, but our understanding of how they achieve this without rigid components remains incomplete. Here, we develop new all-optical methods based on optical interference in a deformable substrate to measure ground reaction forces (GRFs) with micrometre and nanonewton precision in behaving Drosophila larvae. Combining this with a kinematic analysis of substrate-interfacing features, we shed new light onto the biomechanical control of larval locomotion. Crawling in larvae measuring ~1 mm in length involves an intricate pattern of cuticle sequestration and planting, producing GRFs of 1–7 µN. We show that larvae insert and expand denticulated, feet-like structures into substrates as they move, a process not previously observed in soft-bodied animals. These ‘protopodia’ form dynamic anchors to compensate counteracting forces. Our work provides a framework for future biomechanics research in soft-bodied animals and promises to inspire improved soft-robot design.

    1. Physics of Living Systems
    Nicholas LaBerge, Kenneth Hunter Wapman ... Daniel B Larremore
    Research Article

    Despite long-running efforts to increase gender diversity among tenured and tenure-track faculty in the U.S., women remain underrepresented in most academic fields, sometimes dramatically so. Here, we quantify the relative importance of faculty hiring and faculty attrition for both past and future faculty gender diversity using comprehensive data on the training and employment of 268,769 tenured and tenure-track faculty rostered at 12,112U.S. PhD-granting departments, spanning 111 academic fields between 2011 and 2020. Over this time, we find that hiring had a far greater impact on women’s representation among faculty than attrition in the majority (90.1%) of academic fields, even as academia loses a higher share of women faculty relative to men at every career stage. Finally, we model the impact of five specific policy interventions on women’s representation, and project that eliminating attrition differences between women and men only leads to a marginal increase in women’s overall representation—in most fields, successful interventions will need to make substantial and sustained changes to hiring in order to reach gender parity.