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

eLife

Angela Taddei¹  Judith Miné-Hattab¹  Aleksandra M Walczak²  Thierry Mora²  Mathias L Heltberg³ 

[1] Institut Curie, CNRS, PSL University, Sorbonne Université, Paris, France;Laboratoire de physique de l’École normale supérieure, CNRS, PSL University, Sorbonne Université, and Université de Paris, Paris, France;Laboratoire de physique de l’École normale supérieure, CNRS, PSL University, Sorbonne Université, and Université de Paris, Paris, France;Institut Curie, CNRS, PSL University, Sorbonne Université, Paris, France;

关键词: membrane-less sub-compartments;    liquid droplet;    polymer binding model;    liquid-liquid phase separation;    cellular foci;    S. cerevisiae;   

DOI  :  10.7554/eLife.69181

来源: eLife Sciences Publications, Ltd

【 摘 要 】

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.

【 授权许可】

CC BY