Optimal reliability, robustness and control of nucleus centering in fission yeast is contingent on nonequilibrium force patterning

Abstract

Cells, such as fission yeast, center their division apparatus to ensure symmetric cell division, a challenging task when the governing dynamics is stochastic. Here we show that the spindle pole body (SPB) positioning, which defines the division septum, is controlled by the patterning of nonequilibrium polymerization forces of microtubule (MT) bundles. We define two cellular objectives, reliability, the mean SPB position relative to the geometric center, and robustness, the variance of the SPB position, which are sensitive to genetic perturbations that change cell length, MT-bundle number/orientation and MT dynamics. We show that the optimal control of reliability and robustness required to minimize septum positioning error is achieved by the wild-type (WT). A stochastic model for the MT-based nucleus centering, with parameters measured directly or estimated using Bayesian inference, recapitulates WT optimality. We use this to perform a sensitivity analysis of the parameters that control nuclear centering.