Quantitative theory for the diffusive dynamics of liquid condensates

  1. Lars Hubatsch
  2. Louise M Jawerth
  3. Celina Love
  4. Jonathan Bauermann
  5. TY Dora Tang
  6. Stefano Bo
  7. Anthony A Hyman
  8. Christoph A Weber  Is a corresponding author
  1. Max Planck Institute for the Physics of Complex Systems, Germany
  2. Max Planck Institute of Molecular Cell Biology and Genetics, Germany

Abstract

Key processes of biological condensates are diffusion and material exchange with their environment. Experimentally, diffusive dynamics are typically probed via fluorescent labels. However, to date, a physics-based, quantitative framework for the dynamics of labeled condensate components is lacking. Here we derive the corresponding dynamic equations, building on the physics of phase separation, and quantitatively validate the related framework via experiments. We show that by using our framework we can precisely determine diffusion coefficients inside liquid condensates via a spatio-temporal analysis of fluorescence recovery after photobleaching (FRAP) experiments. We showcase the accuracy and precision of our approach by considering space- and time-resolved data of protein condensates and two different polyelectrolyte-coacervate systems. Interestingly, our theory can also be used to determine a relationship between the diffusion coefficient in the dilute phase and the partition coefficient, without relying on fluorescence measurements in the dilute phase. This enables us to investigate the effect of salt addition on partitioning and bypasses recently described quenching artifacts in the dense phase. Our approach opens new avenues for theoretically describing molecule dynamics in condensates, measuring concentrations based on the dynamics of fluorescence intensities, and quantifying rates of biochemical reactions in liquid condensates.

Data availability

Code for modelling and data analysis is available at https://gitlab.pks.mpg.de/mesoscopic-physics-of-life/frap_theory and https://gitlab.pks.mpg.de/mesoscopic-physics-of-life/frap_analysis .

Article and author information

Author details

  1. Lars Hubatsch

    Biological Physics, Max Planck Institute for the Physics of Complex Systems, Dresden, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1934-7437
  2. Louise M Jawerth

    Biological Physics, Max Planck Institute for the Physics of Complex Systems, Dresden, Germany
    Competing interests
    The authors declare that no competing interests exist.
  3. Celina Love

    Dynamic Protocellular Systems, Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
    Competing interests
    The authors declare that no competing interests exist.
  4. Jonathan Bauermann

    Biological Physics, Max Planck Institute for the Physics of Complex Systems, Dresden, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0301-7655
  5. TY Dora Tang

    Dynamic Protocellular Systems, Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
    Competing interests
    The authors declare that no competing interests exist.
  6. Stefano Bo

    Biological Physics, Max Planck Institute for the Physics of Complex Systems, Dresden, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2738-867X
  7. Anthony A Hyman

    Dynamic Protocellular Systems, Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
    Competing interests
    The authors declare that no competing interests exist.
  8. Christoph A Weber

    Biological Physics, Max Planck Institute for the Physics of Complex Systems, Dresden, Germany
    For correspondence
    weber@pks.mpg.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6279-0405

Funding

Deutsche Forschungsgemeinschaft (SPP 2191)

  • Lars Hubatsch
  • Anthony A Hyman
  • Christoph A Weber

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

Reviewing Editor

  1. Rohit V Pappu, Washington University in St Louis, United States

Version history

  1. Preprint posted: March 8, 2021 (view preprint)
  2. Received: March 21, 2021
  3. Accepted: October 11, 2021
  4. Accepted Manuscript published: October 12, 2021 (version 1)
  5. Version of Record published: November 10, 2021 (version 2)

Copyright

© 2021, Hubatsch 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.

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  1. Lars Hubatsch
  2. Louise M Jawerth
  3. Celina Love
  4. Jonathan Bauermann
  5. TY Dora Tang
  6. Stefano Bo
  7. Anthony A Hyman
  8. Christoph A Weber
(2021)
Quantitative theory for the diffusive dynamics of liquid condensates
eLife 10:e68620.
https://doi.org/10.7554/eLife.68620

Share this article

https://doi.org/10.7554/eLife.68620

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