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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eLife Sciences Publications Ltd
2021
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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) |
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membrane-less sub-compartments liquid droplet polymer binding model liquid-liquid phase separation cellular foci Medicine R Science Q Biology (General) QH301-705.5 |
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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 |
_version_ |
1718425408871858176 |