1. Physics of Living Systems
Download icon

Charge-driven condensation of RNA and proteins suggests broad role of phase separation in cytoplasmic environments

Research Article
  • Cited 1
  • Views 4,381
  • Annotations
Cite this article as: eLife 2021;10:e64004 doi: 10.7554/eLife.64004

Abstract

Phase separation processes are increasingly being recognized as important organizing mechanisms of biological macromolecules in cellular environments. Well established drivers of phase separation are multi-valency and intrinsic disorder. Here, we show that globular macromolecules may condense simply based on electrostatic complementarity. More specifically, phase separation of mixtures between RNA and positively charged proteins is described from a combination of multiscale computer simulations with microscopy and spectroscopy experiments. Phase diagrams were mapped out as a function of molecular concentrations in experiment and as a function of molecular size and temperature via simulations. The resulting condensates were found to retain at least some degree of internal dynamics varying as a function of the molecular composition. The results suggest a more general principle for phase separation that is based primarily on electrostatic complementarity without invoking polymer properties as in most previous studies. Simulation results furthermore suggest that such phase separation may occur widely in heterogenous cellular environment between nucleic acid and protein components.

Data availability

All experimental data generated and analyzed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Bercem Dutagaci

    Biochemistry & Molecular Biology, Michigan State University, East Lansing, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0333-5757
  2. Grzegorz Nawrocki

    Biochemistry & Molecular Biology, Michigan State University, East Lansing, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Joyce Goodluck

    Physics, Michigan State University, East Lansing, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Ali Akbar Ashkarran

    Precision Health Program and Department of Radiology, Michigan State University, East Lansing, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Charles G Hoogstraten

    Biochemistry & Molecular Biology, Michigan State University, East Lansing, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Lisa J Lapidus

    Physics, Michigan State University, East Lansing, United States
    For correspondence
    lapidus@msu.edu
    Competing interests
    The authors declare that no competing interests exist.
  7. Michael Feig

    Biochemistry & Molecular Biology, Michigan State University, East Lansing, United States
    For correspondence
    mfeiglab@gmail.com
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9380-6422

Funding

National Institutes of Health (R35 GM126948)

  • Bercem Dutagaci
  • Grzegorz Nawrocki
  • Michael Feig

National Science Foundation (MCB 1817307)

  • Bercem Dutagaci
  • Grzegorz Nawrocki
  • Joyce Goodluck
  • Lisa J Lapidus
  • Michael Feig

National Science Foundation (MCB 2018296)

  • Charles G Hoogstraten

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

Reviewing Editor

  1. Donald Hamelberg, Georgia State University, United States

Publication history

  1. Received: October 15, 2020
  2. Accepted: January 25, 2021
  3. Accepted Manuscript published: January 26, 2021 (version 1)
  4. Version of Record published: February 10, 2021 (version 2)

Copyright

© 2021, Dutagaci 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

  • 4,381
    Page views
  • 515
    Downloads
  • 1
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

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)

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

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

Further reading

    1. Cell Biology
    2. Physics of Living Systems
    Sohyeon Park et al.
    Research Article Updated

    In addition to diffusive signals, cells in tissue also communicate via long, thin cellular protrusions, such as airinemes in zebrafish. Before establishing communication, cellular protrusions must find their target cell. Here, we demonstrate that the shapes of airinemes in zebrafish are consistent with a finite persistent random walk model. The probability of contacting the target cell is maximized for a balance between ballistic search (straight) and diffusive search (highly curved, random). We find that the curvature of airinemes in zebrafish, extracted from live-cell microscopy, is approximately the same value as the optimum in the simple persistent random walk model. We also explore the ability of the target cell to infer direction of the airineme’s source, finding that there is a theoretical trade-off between search optimality and directional information. This provides a framework to characterize the shape, and performance objectives, of non-canonical cellular protrusions in general.

    1. Cell Biology
    2. Physics of Living Systems
    Larisa Venkova et al.
    Research Article Updated

    Mechanics has been a central focus of physical biology in the past decade. In comparison, how cells manage their size is less understood. Here, we show that a parameter central to both the physics and the physiology of the cell, its volume, depends on a mechano-osmotic coupling. We found that cells change their volume depending on the rate at which they change shape, when they spontaneously spread or when they are externally deformed. Cells undergo slow deformation at constant volume, while fast deformation leads to volume loss. We propose a mechanosensitive pump and leak model to explain this phenomenon. Our model and experiments suggest that volume modulation depends on the state of the actin cortex and the coupling of ion fluxes to membrane tension. This mechano-osmotic coupling defines a membrane tension homeostasis module constantly at work in cells, causing volume fluctuations associated with fast cell shape changes, with potential consequences on cellular physiology.