Bistability and oscillations in cooperative microtubule and kinetochore dynamics in the mitotic spindle
Bistability and oscillations in cooperative microtubule and kinetochore dynamics in the mitotic spindle
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DOI：
10.1088/1367-2630/ab7ede
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发表时间：
2019-03
影响因子：
3.3
通讯作者：
Felix Schwietert;J. Kierfeld
中科院分区：
文献类型：
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作者：
Felix Schwietert;J. Kierfeld
在有丝分裂纺锤体微管附着在着丝粒通过捕捉键在中期，微管解聚力引起随机染色体振荡。我们调查的合作随机微管动力学的纺锤体模型组成的合奏的平行微管，通过弹性连接器连接到动粒。我们包括动态不稳定性的微管和力的微管和动粒从弹性连接。一个片面的模型，其中外力作用在动粒上解析求解采用平均场方法的基础上福克-普朗克方程。该解决方案建立了微管系综与随机模拟一致的摩擦力-速度关系。我们推导出连接器的刚度和微管数量的双稳态约束。单侧纺锤体模型的力-速度关系引起双侧模型的振荡，这可以解释染色体在中期的随机振荡（方向不稳定性）。我们推导出的链接器的刚度和微管数目中期染色体振荡的限制。包括极向微管通量到模型中，我们可以提供一个解释的实验观察到的抑制细胞中的染色体振荡与高极向通量速度。然而，在极性喷射力的存在下，染色体振荡持续存在，振幅减小，并且在姐妹动粒之间存在相移。此外，极性弹射力是必要的，以调整染色体在纺锤体赤道和稳定的交替振荡模式的两个动粒。最后，我们修改了模型，使微管只能施加张力的动粒导致拔河的两个微管合奏之间的战争。然后，到达动粒后的诱导微管灾难是刺激振荡所必需的。该模型可以定量再现PtK 1细胞动粒振荡的实验结果。
In the mitotic spindle microtubules attach to kinetochores via catch bonds during metaphase, and microtubule depolymerization forces give rise to stochastic chromosome oscillations. We investigate the cooperative stochastic microtubule dynamics in spindle models consisting of ensembles of parallel microtubules, which attach to a kinetochore via elastic linkers. We include the dynamic instability of microtubules and forces on microtubules and kinetochores from elastic linkers. A one-sided model, where an external force acts on the kinetochore is solved analytically employing a mean-field approach based on Fokker–Planck equations. The solution establishes a bistable force–velocity relation of the microtubule ensemble in agreement with stochastic simulations. We derive constraints on linker stiffness and microtubule number for bistability. The bistable force–velocity relation of the one-sided spindle model gives rise to oscillations in the two-sided model, which can explain stochastic chromosome oscillations in metaphase (directional instability). We derive constraints on linker stiffness and microtubule number for metaphase chromosome oscillations. Including poleward microtubule flux into the model we can provide an explanation for the experimentally observed suppression of chromosome oscillations in cells with high poleward flux velocities. Chromosome oscillations persist in the presence of polar ejection forces, however, with a reduced amplitude and a phase shift between sister kinetochores. Moreover, polar ejection forces are necessary to align the chromosomes at the spindle equator and stabilize an alternating oscillation pattern of the two kinetochores. Finally, we modify the model such that microtubules can only exert tensile forces on the kinetochore resulting in a tug-of-war between the two microtubule ensembles. Then, induced microtubule catastrophes after reaching the kinetochore are necessary to stimulate oscillations. The model can reproduce experimental results for kinetochore oscillations in PtK1 cells quantitatively.