Mechanism of inter-chromosome attraction driven by a localized charged patch
Abstract:
The coacervation of charged polymers has been proposed as 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 formation of RNA bridges between the chromosome surfaces, which are coated by brushes of Ki-67, a charged intrinsically disordered protein. RNA bridging has been shown to be specifically promoted by a strongly localized charged patch on Ki-67 [2], although the physical details of this mechanism remain unclear. To elucidate this process, we employ here coarse-grained simulations and analytical theory to study the bridging interaction between charged polymer brushes. We compare uniformly charged brushes to ones with the same total charge, but a fraction of it focused on a patch. Our simulations reveal that for uniformly charged brushes, bridging is basically absent due to complete adsorption of RNA onto the brush. Stable bridging is only observed for brushes with charged patches, where the interaction with RNA is both strong and localized. We also show that the charged patch leads to dynamical caging of the RNA molecules, and thus to a significant increase in the viscosity of the Ki-67/RNA condensate. This suggests that localized charges can be one of the mechanism that contribute to the high viscosity of biomolecular condensates measured in experiments. Overall, our work elucidates the physical mechanism leading to chromosome clustering, and emphasizes the importance of localized interactions for the formation and stability of biomolecular condensates.
[1] S. Cuylen-Haering, M. Petrovic, A. Hernandez-Armendariz, M. W. Schneider, M. Samwer, C. Blaukopf, L. J. Holt, and D. W. Gerlich, Chromosome clustering by Ki-67 excludes cytoplasm during nuclear assembly, Nature 587, 285 (2020)
[2] A. Hernandez-Armendariz, V. Sorichetti, Y. Hayashi, Z. Koskova, A. Brunner, J. Ellenberg, A. Šarić, and S. Cuylen-Haering, A liquid-like coat mediates chromosome clustering during mitotic exit, Molecular Cell 84, 3254 (2024).
Abstract:
The coacervation of charged polymers has been proposed as 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 formation of RNA bridges between the chromosome surfaces, which are coated by brushes of Ki-67, a charged intrinsically disordered protein. RNA bridging has been shown to be specifically promoted by a strongly localized charged patch on Ki-67 [2], although the physical details of this mechanism remain unclear. To elucidate this process, we employ here coarse-grained simulations and analytical theory to study the bridging interaction between charged polymer brushes. We compare uniformly charged brushes to ones with the same total charge, but a fraction of it focused on a patch. Our simulations reveal that for uniformly charged brushes, bridging is basically absent due to complete adsorption of RNA onto the brush. Stable bridging is only observed for brushes with charged patches, where the interaction with RNA is both strong and localized. We also show that the charged patch leads to dynamical caging of the RNA molecules, and thus to a significant increase in the viscosity of the Ki-67/RNA condensate. This suggests that localized charges can be one of the mechanism that contribute to the high viscosity of biomolecular condensates measured in experiments. Overall, our work elucidates the physical mechanism leading to chromosome clustering, and emphasizes the importance of localized interactions for the formation and stability of biomolecular condensates.
[1] S. Cuylen-Haering, M. Petrovic, A. Hernandez-Armendariz, M. W. Schneider, M. Samwer, C. Blaukopf, L. J. Holt, and D. W. Gerlich, Chromosome clustering by Ki-67 excludes cytoplasm during nuclear assembly, Nature 587, 285 (2020)
[2] A. Hernandez-Armendariz, V. Sorichetti, Y. Hayashi, Z. Koskova, A. Brunner, J. Ellenberg, A. Šarić, and S. Cuylen-Haering, A liquid-like coat mediates chromosome clustering during mitotic exit, Molecular Cell 84, 3254 (2024).
