Physical observables to determine the nature of membrane-less cellular sub-compartments
- Institut Curie, France
- Institut Curie, PSL University, Sorbonne Université, CNRS, Nuclear Dynamics, France
- 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.
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All data generated or analysed during this study are included in the manuscript and supporting files.
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Author details
Judith Miné-Hattab
Aleksandra M Walczak
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.
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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Physical observables to determine the nature of membrane-less cellular sub-compartments
eLife 10:e69181.
https://doi.org/10.7554/eLife.69181
