Physical observables to determine the nature of membrane-less cellular sub-compartments

  1. Mathias L Heltberg
  2. Judith Miné-Hattab
  3. Angela Taddei
  4. Aleksandra M Walczak  Is a corresponding author
  5. Thierry Mora  Is a corresponding author
  1. Institut Curie, France
  2. Institut Curie, PSL University, Sorbonne Université, CNRS, Nuclear Dynamics, France
  3. École Normale Supérieure, France

Abstract

The spatial organization of complex biochemical reactions is essential for the regulation of cellular processes. Membrane-less structures called foci containing high concentrations of specific proteins have been reported in a variety of contexts, but the mechanism of their formation is not fully understood. Several competing mechanisms exist that are difficult to distinguish empirically, including liquid-liquid phase separation, and the trapping of molecules by multiple binding sites. Here we propose a theoretical framework and outline observables to differentiate between these scenarios from single molecule tracking experiments. In the binding site model, we derive relations between the distribution of proteins, their diffusion properties, and their radial displacement. We predict that protein search times can be reduced for targets inside a liquid droplet, but not in an aggregate of slowly moving binding sites. We use our results to reject the multiple binding site model for Rad52 foci, and find a picture consistent with a liquid-liquid phase separation. These results are applicable to future experiments and suggest different biological roles for liquid droplet and binding site foci.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files.

The following previously published data sets were used

Article and author information

Author details

  1. Mathias L Heltberg

    UMR 3664 - Nuclear Dynamics, Institut Curie, paris, France
    Competing interests
    No competing interests declared.
  2. Judith Miné-Hattab

    Institut Curie, PSL University, Sorbonne Université, CNRS, Nuclear Dynamics, Paris, France
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9986-4092
  3. Angela Taddei

    UMR3664, Institut Curie, Paris, France
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3217-0739
  4. Aleksandra M Walczak

    Laboratoire de Physique Theorique, École Normale Supérieure, Paris, France
    For correspondence
    aleksandra.walczak@phys.ens.fr
    Competing interests
    Aleksandra M Walczak, eLife senior editor.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2686-5702
  5. Thierry Mora

    Laboratoire de Physique Theorique, École Normale Supérieure, Paris, France
    For correspondence
    thierry.mora@gmail.com
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5456-9361

Funding

Agence Nationale de la Recherche (Q-life 356 ANR-17-CONV-0005)

  • Mathias L Heltberg
  • Judith Miné-Hattab
  • Angela Taddei
  • Aleksandra M Walczak
  • Thierry Mora

Centre National de la Recherche Scientifique (80' MITI project PhONeS)

  • Judith Miné-Hattab
  • Angela Taddei

H2020 European Research Council (COG 724208)

  • Mathias L Heltberg
  • Aleksandra M Walczak
  • Thierry Mora

Agence Nationale de la Recherche (ANR-15-CE12-0007)

  • Judith Miné-Hattab
  • Angela Taddei

Agence Nationale de la Recherche (ANR-12-PDOC- 0035?01)

  • Judith Miné-Hattab
  • Angela Taddei

Fondation pour la Recherche Médicale (DEP20151234398)

  • Judith Miné-Hattab
  • Angela Taddei

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

Reviewing Editor

  1. Agnese Seminara, University of Genoa, Italy

Publication history

  1. Received: April 7, 2021
  2. Accepted: October 21, 2021
  3. Accepted Manuscript published: October 22, 2021 (version 1)
  4. Version of Record published: November 17, 2021 (version 2)

Copyright

© 2021, Heltberg 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. Mathias L Heltberg
  2. Judith Miné-Hattab
  3. Angela Taddei
  4. Aleksandra M Walczak
  5. Thierry Mora
(2021)
Physical observables to determine the nature of membrane-less cellular sub-compartments
eLife 10:e69181.
https://doi.org/10.7554/eLife.69181

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