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

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 und...

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Autores principales: Mathias L Heltberg, Judith Miné-Hattab, Angela Taddei, Aleksandra M Walczak, Thierry Mora
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Lenguaje:EN
Publicado: eLife Sciences Publications Ltd 2021
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Acceso en línea:https://doaj.org/article/3fbcc40c70814c5094e063f34bb47674
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spelling oai:doaj.org-article:3fbcc40c70814c5094e063f34bb476742021-11-17T14:32:12ZPhysical observables to determine the nature of membrane-less cellular sub-compartments10.7554/eLife.691812050-084Xe69181https://doaj.org/article/3fbcc40c70814c5094e063f34bb476742021-10-01T00:00:00Zhttps://elifesciences.org/articles/69181https://doaj.org/toc/2050-084XThe 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.Mathias L HeltbergJudith Miné-HattabAngela TaddeiAleksandra M WalczakThierry MoraeLife Sciences Publications Ltdarticlemembrane-less sub-compartmentsliquid dropletpolymer binding modelliquid-liquid phase separationcellular fociMedicineRScienceQBiology (General)QH301-705.5ENeLife, Vol 10 (2021)
institution DOAJ
collection DOAJ
language EN
topic membrane-less sub-compartments
liquid droplet
polymer binding model
liquid-liquid phase separation
cellular foci
Medicine
R
Science
Q
Biology (General)
QH301-705.5
spellingShingle membrane-less sub-compartments
liquid droplet
polymer binding model
liquid-liquid phase separation
cellular foci
Medicine
R
Science
Q
Biology (General)
QH301-705.5
Mathias L Heltberg
Judith Miné-Hattab
Angela Taddei
Aleksandra M Walczak
Thierry Mora
Physical observables to determine the nature of membrane-less cellular sub-compartments
description 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.
format article
author Mathias L Heltberg
Judith Miné-Hattab
Angela Taddei
Aleksandra M Walczak
Thierry Mora
author_facet Mathias L Heltberg
Judith Miné-Hattab
Angela Taddei
Aleksandra M Walczak
Thierry Mora
author_sort Mathias L Heltberg
title Physical observables to determine the nature of membrane-less cellular sub-compartments
title_short Physical observables to determine the nature of membrane-less cellular sub-compartments
title_full Physical observables to determine the nature of membrane-less cellular sub-compartments
title_fullStr Physical observables to determine the nature of membrane-less cellular sub-compartments
title_full_unstemmed Physical observables to determine the nature of membrane-less cellular sub-compartments
title_sort physical observables to determine the nature of membrane-less cellular sub-compartments
publisher eLife Sciences Publications Ltd
publishDate 2021
url https://doaj.org/article/3fbcc40c70814c5094e063f34bb47674
work_keys_str_mv AT mathiaslheltberg physicalobservablestodeterminethenatureofmembranelesscellularsubcompartments
AT judithminehattab physicalobservablestodeterminethenatureofmembranelesscellularsubcompartments
AT angelataddei physicalobservablestodeterminethenatureofmembranelesscellularsubcompartments
AT aleksandramwalczak physicalobservablestodeterminethenatureofmembranelesscellularsubcompartments
AT thierrymora physicalobservablestodeterminethenatureofmembranelesscellularsubcompartments
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