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1.
Mol Cell ; 84(17): 3254-3270.e9, 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39153474

RESUMO

The individualization of chromosomes during early mitosis and their clustering upon exit from cell division are two key transitions that ensure efficient segregation of eukaryotic chromosomes. Both processes are regulated by the surfactant-like protein Ki-67, but how Ki-67 achieves these diametric functions has remained unknown. Here, we report that Ki-67 radically switches from a chromosome repellent to a chromosome attractant during anaphase in human cells. We show that Ki-67 dephosphorylation during mitotic exit and the simultaneous exposure of a conserved basic patch induce the RNA-dependent formation of a liquid-like condensed phase on the chromosome surface. Experiments and coarse-grained simulations support a model in which the coalescence of chromosome surfaces, driven by co-condensation of Ki-67 and RNA, promotes clustering of chromosomes. Our study reveals how the switch of Ki-67 from a surfactant to a liquid-like condensed phase can generate mechanical forces during genome segregation that are required for re-establishing nuclear-cytoplasmic compartmentalization after mitosis.


Assuntos
Segregação de Cromossomos , Cromossomos Humanos , Antígeno Ki-67 , Mitose , Humanos , Antígeno Ki-67/metabolismo , Antígeno Ki-67/genética , Células HeLa , Cromossomos Humanos/metabolismo , Cromossomos Humanos/genética , Fosforilação , Anáfase
2.
Phys Rev Lett ; 131(22): 228401, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-38101392

RESUMO

The kinetics of the assembly of semiflexible filaments through end-to-end annealing is key to the structure of the cytoskeleton, but is not understood. We analyze this problem through scaling theory and simulations, and uncover a regime where filaments' ends find each other through bending fluctuations without the need for the whole filament to diffuse. This results in a very substantial speedup of assembly in physiological regimes, and could help with understanding the dynamics of actin and intermediate filaments in biological processes such as wound healing and cell division.


Assuntos
Actinas , Citoesqueleto , Actinas/química , Filamentos Intermediários , Microtúbulos , Citoesqueleto de Actina/química
3.
J Chem Phys ; 158(7): 074905, 2023 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-36813705

RESUMO

The elasticity of disordered and polydisperse polymer networks is a fundamental problem of soft matter physics that is still open. Here, we self-assemble polymer networks via simulations of a mixture of bivalent and tri- or tetravalent patchy particles, which result in an exponential strand length distribution analogous to that of experimental randomly cross-linked systems. After assembly, the network connectivity and topology are frozen and the resulting system is characterized. We find that the fractal structure of the network depends on the number density at which the assembly has been carried out, but that systems with the same mean valence and same assembly density have the same structural properties. Moreover, we compute the long-time limit of the mean-squared displacement, also known as the (squared) localization length, of the cross-links and of the middle monomers of the strands, showing that the dynamics of long strands is well described by the tube model. Finally, we find a relation connecting these two localization lengths at high density and connect the cross-link localization length to the shear modulus of the system.

4.
Macromolecules ; 54(8): 3769-3779, 2021 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-34054144

RESUMO

Due to their unique structural and mechanical properties, randomly cross-linked polymer networks play an important role in many different fields, ranging from cellular biology to industrial processes. In order to elucidate how these properties are controlled by the physical details of the network (e.g., chain-length and end-to-end distributions), we generate disordered phantom networks with different cross-linker concentrations C and initial densities ρinit and evaluate their elastic properties. We find that the shear modulus computed at the same strand concentration for networks with the same C, which determines the number of chains and the chain-length distribution, depends strongly on the preparation protocol of the network, here controlled by ρinit. We rationalize this dependence by employing a generic stress-strain relation for polymer networks that does not rely on the specific form of the polymer end-to-end distance distribution. We find that the shear modulus of the networks is a nonmonotonic function of the density of elastically active strands, and that this behavior has a purely entropic origin. Our results show that if short chains are abundant, as it is always the case for randomly cross-linked polymer networks, the knowledge of the exact chain conformation distribution is essential for correctly predicting the elastic properties. Finally, we apply our theoretical approach to literature experimental data, qualitatively confirming our interpretations.

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