Principles of spindle size regulation and scaling

How cells control the size and morphology of their internal structures is an open and central question in biology. While the size of most intracellular structures scales with cell size - larger cells tend to have a larger nucleus and mitotic spindles - it is unclear what aspect of cell size sets the scaling and how. Here, we provide a mechanistic explanation for scaling the first mitotic spindle with cell size in C. elegans. We used a combination of quantitative microscopy and biophysical perturbations to establish the importance of a balance of cortical pulling forces in the regulation of spindle length and dynamics. This led us to construct a model for which the stoichiometric interactions of microtubules and cortical force generators (each force generator can bind only one microtubule) is key to explaining the dynamics of spindle positioning, its elongation, and length scaling with cell length. This model accounts for variations in all the spindle traits we studied here, both within species and across nematode species spanning over 100 million years of evolution.