Signaling and mechanics in mitotic spindle assembly

During mitosis a bipolar spindle structure is assembled in the cell to equally partition the duplicated genetic material into daughter cells. Faulty spindle assembly can cause genomic errors that kill the cell or promote cancer development. Proper spindle assembly relies on the coordinated activities of numerous molecules that play different roles, from structure and mechanics to signaling and quality surveillance. In this talk I will introduce our recent theoretical modeling in both the signaling and mechanical aspects of spindle assembly. For signaling, we modeled the intracellular spatiotemporal dynamics of the spindle assembly checkpoint proteins – molecules that survey the attachments between the chromosomes and the spindle. Our model proposes a novel mechanistic link between the observed spatial regulation of the checkpoint proteins and noise robustness of the checkpoint silencing process. The model provides mechanistic explanations for many intriguing mitotic phenomena, for instance, how the checkpoint mechanism facilitates bipolar spindle assembly in cancer cells with extra centrosomes. Furthermore, in the mechanical aspect, we modeled the mechanical dynamics that drives the movements of centrosomes in a mitotic cell and examined the resulting spindle geometry. Our model predicts the most critical biophysical factors that enable bipolar spindle formation in the presence of both normal and extra centrosome numbers.