A Typical Workflow to Simulate Cytoskeletal Systems

Lugo, Carlos A.; Saikia, Eashan; Nédélec, François

doi:10.3791/64125

Cited by 6 publications

(2 citation statements)

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“…To gain further insight into the force generating properties of EB/HSET system and understand how it could facilitate stabilization of the bipolar configuration, we used the open source software package Cytosim. 52 We simulated the interaction between two 2D asters of microtubules in the presence of HSET motors and EB. Microtubules were modelled as elastic rods with their minus fixed at one of the two microtubule nucleation centers, and dynamic plus ends.…”

Section: Resultsmentioning

confidence: 99%

Force-transducing molecular ensembles at growing microtubule tips control mitotic spindle size

Chu,

Stedman,

Gannon

et al. 2024

Preprint

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Mitotic spindle is a complex bipolar cellular structure that ensures chromosomes segregation between dividing cells. Correct spindle size is required for the accurate segregation and successful passing of genomes to the newly formed cells. The spindle size is believed to be controlled by mechanical forces generated by molecular motors and non-motor proteins acting in the spindle microtubule overlaps. However, how forces generated by individual proteins enable bipolar spindle organization is not well understood. Here, we developed tools to measure contributions of individual molecules to this force balance. We show that microtubule tip-trackers act synergetically at microtubule tips with minus-end directed motors to produce a system that can generate both pushing and pulling forces. We show that this system harnesses forces generated by growing tips of spindle microtubules and provides unique contribution to the force balance distinct from other force generators because it acts at microtubule tips rather than in microtubule overlaps. We show that this system alone can establish stable bipolar organization in vitro and in mitotic spindles in human cells. Our results pave the way for understanding how mechanical forces in spindles can be fine-tuned to control the fidelity of chromosome segregation.

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Section: Resultsmentioning

confidence: 99%

Force-transducing molecular ensembles at growing microtubule tips control mitotic spindle size

Chu,

Stedman,

Gannon

et al. 2024

Preprint

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“…We used Cytosim, an agent-based modeling framework, (41,46,(55)(56)(57) to model dynamics of the actin filaments confined within an actin droplet at non-equilibrium steady state and investigated how different kinetic time scales including binding and unbinding of actin to VASP, and actin elongation rate affect the formation of actin shells and rings. Our simulations showed that the distribution of rings and shells is determined by the competition between binding and unbinding kinetics of actin and VASP.…”

Section: Introductionmentioning

confidence: 99%

Kinetic trapping organizes actin filaments within liquid-like protein droplets

Chandrasekaran

Graham

Stachowiak

et al. 2023

Preprint

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Actin is essential for various cellular functions such as growth, migration, and endocytosis. Recent evidence suggests that several actin-binding proteins phase separate to form condensates and that actin networks have different architectures in these droplets. In this study, we use computational modeling to investigate the conditions under which actin forms different network organizations in VASP droplets. Our simulations reveal that the binding and unbinding rates of actin and VASP determine the probability of formation of shells and rings, with shells being more probable than rings. The different actin networks are highly dependent on the kinetics of VASP-actin interactions, suggesting that they arise from kinetic trapping. Specifically, we showed that reducing the residence time of VASP on actin filaments promotes assembly of shells rather than rings, where rings require a greater degree of actin bundling. These predictions were tested experimentally using a mutant of VASP, which has decreased bundling capability. Experiments reveal an increase in the abundance of shells in VASP droplets, consistent with our predictions. Finally, we investigated the arrangements of filaments within deformed droplets and found that the filament length largely determines whether a droplet will straighten into a bundle or remain kinetically trapped in a ring-like architecture. The sphere-to-ellipsoid transition is favored under a wide range of conditions while the ellipse-to-rod transition is only permitted when filaments have a specific range of lengths. Our findings have implications for understanding how the interactions between phase-separated actin binding proteins and actin filaments can give rise to different actin network architectures.

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Force-transducing molecular ensembles at growing microtubule tips control mitotic spindle size

Chu,

Stedman,

Gannon

et al. 2024

Nat Commun

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Correct mitotic spindle size is required for accurate chromosome segregation during cell division. It is controlled by mechanical forces generated by molecular motors and non-motor proteins acting on spindle microtubules. However, how forces generated by individual proteins enable bipolar spindle organization is not well understood. Here, we develop tools to measure contributions of individual molecules to this force balance. We show that microtubule plus-end binding proteins act at microtubule tips synergistically with minus-end directed motors to produce a system that can generate both pushing and pulling forces. To generate pushing force, the system harnesses forces generated by the growing tips of microtubules providing unique contribution to the force balance distinct from all other motors that act in the mitotic spindle. Our results reveal that microtubules are essential force generators for establishing spindle size and pave the way for understanding how mechanical forces can be fine-tuned to control the fidelity of chromosome segregation.

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A Typical Workflow to Simulate Cytoskeletal Systems

Cited by 6 publications

References 0 publications

Force-transducing molecular ensembles at growing microtubule tips control mitotic spindle size

Force-transducing molecular ensembles at growing microtubule tips control mitotic spindle size

Kinetic trapping organizes actin filaments within liquid-like protein droplets

Force-transducing molecular ensembles at growing microtubule tips control mitotic spindle size

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