Modeling reveals cortical dynein-dependent fluctuations in bipolar spindle length

Abstract

<jats:p>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 force components of the mitotic spindle, identifying the implications of force perturbations in the spindle remains a challenge. We developed a computational framework of the minimal force requirements for mitotic progression and used experimental approaches to further define and validate the model. Through simulations, we show that rather than achieving and maintaining a constant bipolar spindle length, oscillations in pole to pole distance occur that coincide with microtubule binding and force generation by cortical dynein. In the context of high kinesin-14 (HSET) activity, we reveal the requirement of high cortical dynein activity for bipolar spindle formation.</jats:p>