Sommaire:

The clustering of eukaryotic chromosomes during mitotic exit is fundamental to ensure that large molecules do not get trapped inside the reforming nuclear envelope. Recent experiments showed that this process is driven by the interaction between the Ki-67 protein brush coating the chromosome surface and RNA. It has also been proposed that a highly charged patch (CP) on Ki-67 is the main driver of Ki-67--RNA attraction. The microscopic physical mechanism behind this attractive interaction remains however not understood. Here, we employ coarse-grained molecular dynamics simulations to study how the interaction between positively charged Ki-67 brushes and negatively charged RNA molecules drives inter-chromosome attraction. To understand the effect of the CP, we compare a system with uniformly charged Ki-67 molecules to one in which part of the molecule's charge is concentrated on a patch. Our model proposes as a possible mechanism of inter-chromosome attraction the formation of RNA bridges between the brushes, that act as entropic springs, pulling the chromosomes together. Additionally, we find that the CP acts as a strong "sticker", favoring the formation of more numerous and long-lived RNA bridges, and thus leading to stronger inter-chromosome attraction compared to uniformly charged Ki-67 molecules. Our work elucidates the physical origin of chromosome clustering, while also suggesting a possible mechanism at play in the formation of intracellular condensates.

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