Proper formation and maintenance of the mitotic spindle is required for faithful cell division. While much work has been done to understand the roles of the key molecular components of the mitotic spindle, identifying the consequences of force perturbations in the spindle remains a challenge. We develop a computational framework accounting for the minimal force requirements of mitotic progression. To reflect early spindle formation, we model microtubule dynamics and interactions with major force-generating motors, excluding chromosome interactions that dominate later in mitosis. We directly integrate our experimental data to define and validate the model. We then use simulations to analyze individual force components over time and their relationship to spindle dynamics, making it distinct from previously published models. We show through both model predictions and biological manipulation that rather than achieving and maintaining a constant bipolar spindle length, fluctuations in pole to pole distance occur that coincide with microtubule binding and force generation by cortical dynein. Our model further predicts that high dynein activity is required for spindle bipolarity when kinesin-14 (HSET) activity is also high. Together, our results provide novel insight into the role of cortical dynein in the regulation of spindle bipolarity.

中文翻译：

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建模揭示了双极心轴长度中皮质动力蛋白依赖性波动。

忠实的细胞分裂需要正确形成和维持有丝分裂纺锤体。尽管已经做了很多工作来了解有丝分裂纺锤体的关键分子成分的作用，但要确定纺锤体中的力扰动的后果仍然是一个挑战。我们开发了一种计算框架，可解决有丝分裂进展所需的最小力量。为了反映早期纺锤体的形成，我们对微管动力学和与主要力产生马达的相互作用进行建模，但不包括在有丝分裂后期占主导地位的染色体相互作用。我们直接整合我们的实验数据来定义和验证模型。然后，我们使用仿真来分析随时间变化的各个力分量及其与主轴动力学的关系，从而使其与以前发布的模型不同。我们通过模型预测和生物学操作都表明，不是达到并保持恒定的双极纺锤体长度，而是发生了杆与杆之间距离的波动，这与微管结合和皮层动力蛋白产生的力一致。我们的模型进一步预测，当驱动蛋白14（HSET）活性也很高时，纺锤体双极性需要高动力蛋白活性。在一起，我们的结果提供了皮层动力蛋白在纺锤体双极性调节中的作用的新颖见解。我们的模型进一步预测，当驱动蛋白14（HSET）活性也很高时，纺锤体双极性需要高动力蛋白活性。在一起，我们的结果提供了皮层动力蛋白在纺锤体双极性调节中的作用的新颖见解。我们的模型进一步预测，当驱动蛋白14（HSET）活性也很高时，纺锤体双极性需要高动力蛋白活性。在一起，我们的结果提供了皮层动力蛋白在纺锤体双极性调节中的作用的新颖见解。