@article{21235, abstract = {The condensation 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. In this process, interchromosome 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. 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. We show that the charged patch on Ki-67 leads to interchromosome 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 with uniform charge. Our work sheds light on the physical origin of chromosome clustering, while also suggesting a general mechanism for cells to tune work production by biomolecular condensates via different charge distributions.}, author = {Sorichetti, Valerio and Robin, Paul and Palaia, Ivan and Hernandez-Armendariz, Alberto and Cuylen-Haering, Sara and Šarić, Anđela}, issn = {2835-8279}, journal = {PRX Life}, number = {3}, publisher = {American Physical Society}, title = {{Charge distribution of the coating brush drives interchromosome attraction}}, doi = {10.1103/41fd-r847}, volume = {3}, year = {2025}, } @article{21256, abstract = {Collagen IV is one of the main components of the basement membrane, a layer of material that lines the majority of tissues in multicellular organisms. Collagen IV molecules assemble into networks, providing stiffness and elasticity to tissues and informing cell and organ shape, especially during development. In this work, we develop two coarse-grained models for collagen IV molecules that retain biochemical bond specificity and coarse grain at different length scales. Through molecular-dynamics simulations, we test the assembly and mechanics of the resulting networks and measure their response to strain in terms of stress, microscopic alignment, and bond dynamics. Within the basement membrane, collagen IV networks rearrange by molecule turnover, which affects tissue organization and can be linked with enzyme activity. Here we explore network rearrangements via bond remodeling, the process of breaking and remaking of bonds between network molecules. We then investigate the effects of active (enzymatic) bond remodeling. We find that this nonequilibrium remodeling allows a network to keep its integrity under strain, while relaxing fully over a variety of timescales, a dynamic response that is unavailable to networks undergoing equilibrium remodeling.}, author = {Meadowcroft, Billie and Sorichetti, Valerio and Ratajczyk, Eryk and Perez Verdugo, Fernanda L and Khalilgharibi, Nargess and Mao, Yanlan and Palaia, Ivan and Šarić, Anđela}, issn = {2835-8279}, journal = {PRX Life}, publisher = {American Physical Society}, title = {{Nonequilibrium remodeling of collagen IV networks in Silico}}, doi = {10.1103/gdd5-rnh7}, volume = {3}, year = {2025}, } @article{20530, abstract = {Cells must coordinate DNA segregation with cytokinesis to ensure that each daughter cell inherits a complete genome. Here, we explore how DNA segregation and division are mechanistically coupled in archaeal relatives of eukaryotes, which lack Cyclin-dependent kinase (CDK)/Cyclins. Using live cell imaging, we first describe the series of sequential changes in DNA organization that accompany cell division in Sulfolobus, which computational modeling shows likely aid genome segregation. Through a perturbation analysis we identify a regulatory checkpoint which ensures that the compaction of the genome into two spatially segregated nucleoids only occurs once cells have assembled a division ring—which also defines the axis of DNA segregation. Finally, we show that DNA compaction and segregation depend, in part, on a ParA homologue, SegA, and its partner SegB, whose absence leads to bridging DNA. Taken together, these data show how regulatory checkpoints like those operating in eukaryotes aid high-fidelity division in an archaeon.}, author = {Parham, Joe and Sorichetti, Valerio and Cezanne, Alice and Foo, Sherman and Kuo, Yin Wei and Hoogenberg, Baukje and Radoux-Mergault, Arthur and Mawdesley, Eloise and Gatward, Lydia Daniels and Boulanger, Jerome and Schulze, Ulrike and Šarić, Anđela and Baum, Buzz}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences}, number = {42}, pages = {e2513939122}, publisher = {National Academy of Sciences}, title = {{Temporal and spatial coordination of DNA segregation and cell division in an archaeon}}, doi = {10.1073/pnas.2513939122}, volume = {122}, year = {2025}, } @article{17050, abstract = {The process of polymer condensation, i.e., the formation of bonds between reactive end groups, is ubiquitous in both industry and biology. Here we study generic systems undergoing polymer condensation in competition with cyclization. Using a generalized Smoluchowski theory, molecular dynamics simulations and experiments with DNA and ATP-consuming T4 ligase, we find that this system displays a transition, from a ring-dominated regime with finite-length chains at infinite time to a linear-polymers-dominated one with chains that keep growing in time. Finally, we show that fluids prepared close to the transition may have widely different compositions and rheology at large condensation times.}, author = {Panoukidou, Maria and Weir, Simon and Sorichetti, Valerio and Fosado, Yair Gutierrez and Lenz, Martin and Michieletto, Davide}, issn = {2643-1564}, journal = {Physical Review Research}, number = {2}, publisher = {American Physical Society}, title = {{Runaway transition in irreversible polymer condensation with cyclization}}, doi = {10.1103/PhysRevResearch.6.023189}, volume = {6}, year = {2024}, } @article{18072, abstract = {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.}, author = {Hernandez-Armendariz, Alberto and Sorichetti, Valerio and Hayashi, Yuki and Koskova, Zuzana and Brunner, Andreas and Ellenberg, Jan and Šarić, Anđela and Cuylen-Haering, Sara}, issn = {1097-4164}, journal = {Molecular Cell}, number = {17}, pages = {P3254--3270.E9}, publisher = {Cell Press}, title = {{A liquid-like coat mediates chromosome clustering during mitotic exit}}, doi = {10.1016/j.molcel.2024.07.022}, volume = {84}, year = {2024}, } @article{12705, abstract = {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.}, author = {Sorichetti, Valerio and Ninarello, Andrea and Ruiz-Franco, José and Hugouvieux, Virginie and Zaccarelli, Emanuela and Micheletti, Cristian and Kob, Walter and Rovigatti, Lorenzo}, issn = {1089-7690}, journal = {Journal of Chemical Physics}, number = {7}, publisher = {American Institute of Physics}, title = {{Structure and elasticity of model disordered, polydisperse, and defect-free polymer networks}}, doi = {10.1063/5.0134271}, volume = {158}, year = {2023}, } @article{14655, abstract = {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.}, author = {Sorichetti, Valerio and Lenz, Martin}, issn = {1079-7114}, journal = {Physical Review Letters}, number = {22}, publisher = {American Physical Society}, title = {{Transverse fluctuations control the assembly of semiflexible filaments}}, doi = {10.1103/PhysRevLett.131.228401}, volume = {131}, year = {2023}, }