论文标题
有丝分裂纺锤体合作微管和动力学动力学的双重性和振荡
Bistability and oscillations in cooperative microtubule and kinetochore dynamics in the mitotic spindle
论文作者
论文摘要
在有丝分裂的纺锤体微管中,通过中期通过捕获键附着在动力学上,微管解聚力会引起随机染色体的振荡。我们研究了由平行微管组成的主轴模型中的合作随机微管动力学,它们通过弹性接头连接到动力学上。我们包括微管的动态不稳定性和弹性接头动力学上的力的动力。一个单方面的模型,其中外力作用在动力学上,通过基于fokker-planck方程的平均场方法进行分析解决。该解决方案与随机模拟一致,建立了微管集合的双速度关系。我们对接头刚度和微管数的限制进行了限制。单侧纺锤体模型的双向力 - 速度关系在双面模型中产生振荡,这可以解释中期(方向不稳定性)中的随机染色体振荡。我们对中期染色体振荡的接头刚度和微管数的限制。将极前的微管磁通包含到模型中,我们可以为在具有高极向速度速度的细胞中实验观察到的抑制染色体振荡提供了解释。然而,染色体振荡持续存在,但是在极地射血力的情况下,振幅降低和姊妹动力学之间的相移。此外,极性弹出力对于在纺锤体赤道处的染色体对齐并稳定两个动力学的交替振荡模式是必需的。最后,我们修改模型,使微管只能在动力学上施加拉伸力,从而导致两个微管集合之间的拔河。然后,到达...
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...