The coacervation of charged polymers is an important driver for the formation of biomolecular condensates. Recent experiments suggest that this mechanism also controls the clustering of eukaryotic chromosomes during the late stages of cell division [1,2]. In this process, inter-chromosome attraction is driven by the condensation of cytoplasmic RNA and Ki-67, a charged intrinsically disordered protein that coats the chromosomes as a brush. Attraction between chromosomes has been shown to be specifically promoted by a localized charged patch on Ki-67, although the physical mechanism remains unclear [2]. To elucidate this process, we combine coarse-grained simulations and analytical theory to study the RNA-mediated interaction between charged polymer brushes on the chromosome surfaces [3]. We find that the charged patch on Ki-67 leads to inter-chromosome attraction via RNA bridging between the two brushes, whereby the RNA preferentially interacts with the charged patches, leading to stable, long-range forces. By contrast, if the brush is uniformly charged, bridging is basically absent due to complete adsorption of RNA onto the brush. Moreover, the RNA dynamics becomes caged in presence of the charged patch, while remaining diffusive when the charge is uniform. Our findings suggest that cells could control the forces exerted by biomolecular condensates by adjusting the way charges are distributed on proteins, providing a potential strategy for regulating biological organization.
References
[1] S. Cuylen-Haering, M. Petrovic, A. Hernandez-Armendariz, M. W. Schneider, M. Samwer, C. Blaukopf, L. J. Holt, and D. W. Gerlich, Nature 587, 285 (2020)
[2] A. Hernandez-Armendariz, V. Sorichetti, Y. Hayashi, Z. Koskova, A. Brunner, J. Ellenberg, A. Šarić, and S. Cuylen-Haering, Molecular Cell 84, 3254 (2024).
[3] V. Sorichetti, P. Robin, I. Palaia, A. Hernandez-Armendariz, S. Cuylen-Haering, A. Šarić, Charge distribution of coating brush drives inter-chromosome attraction, biorXiv 2024.12.01.626236.