Positioning the nucleus at the bud neck during Saccharomyces cerevisiae mitosis involves pulling forces of cytoplasmic dynein localized in the daughter cell. Although genetic analysis has revealed a complex network positioning the nucleus, quantification of the forces acting on the nucleus and the number of dyneins driving the process has remained difficult. To better understand the collective forces involved in nuclear positioning, we compare a model of dyneins-driven microtubule (MT) pulling, MT pushing, and cytoplasmic drag to experiments. During S. cerevisiae mitosis, MTs interacting with the cortex nucleated by the daughter spindle pole body (SPB) (SPB-D) are longer than the mother SPB (SPB-M), increasing further during spindle elongation in anaphase. Interphasic SPB mobility is effectively diffusive, while the mitotic mobility is directed. By optimizing a computational model of the mobility of the nucleus due to diffusion and MTs pushing at the cell membrane to experiment, we estimate the viscosity governing the drag force on nuclei during positioning. A force balance model of mitotic SPB mobility compared to experimental mobility suggests that even one or two dynein dimers are sufficient to move the nucleus in the bud neck. Using stochastic computer simulations of a budding cell, we find that punctate dynein localization can generate sufficient force to reel in the nucleus to the bud neck. Compared to uniform motor localization, puncta involve fewer motors suggesting a functional role for motor clustering. Stochastic simulations also suggest that a higher number of force generators than predicted by force balance may be required to ensure the robustness of spindle positioning.

中文翻译：

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在酿酒酵母有丝分裂期间通过拉动星体微管进行细胞核的集体动力蛋白转运

在酿酒酵母有丝分裂期间将细胞核定位在芽颈处涉及到位于子细胞中的细胞质动力蛋白的拉力。尽管遗传分析揭示了定位核的复杂网络，但对作用于核的力和驱动该过程的动力蛋白数量的量化仍然很困难。为了更好地理解核定位所涉及的集体力量，我们将动力蛋白驱动的微管 (MT) 拉动、MT 推动和细胞质拖动模型与实验进行了比较。在酿酒酵母期间在有丝分裂中，与子体纺锤体极体 (SPB) (SPB-D) 成核的皮质相互作用的 MT 比母体 SPB (SPB-M) 长，在后期纺锤体伸长期间进一步增加。相间 SPB 迁移率是有效扩散的，而有丝分裂迁移率是定向的。通过优化由于扩散和 MT 推动细胞膜进行实验而导致的细胞核迁移率的计算模型，我们估计了在定位过程中控制细胞核阻力的粘度。与实验移动性相比，有丝分裂 SPB 移动性的力平衡模型表明，即使是一两个动力蛋白二聚体也足以移动芽颈中的细胞核。使用萌芽细胞的随机计算机模拟，我们发现点状动力蛋白定位可以产生足够的力将细胞核卷入芽颈。与统一的运动定位相比，斑点涉及较少的运动，表明运动聚类的功能作用。随机模拟还表明，可能需要比力平衡预测的更多的力发生器，以确保主轴定位的稳健性。