iScience (May 2023)
Reliable and robust control of nucleus centering is contingent on nonequilibrium force patterns
Abstract
Summary: Cell centers their division apparatus to ensure symmetric cell division, a challenging task when the governing dynamics is stochastic. Using fission yeast, we show that the patterning of nonequilibrium polymerization forces of microtubule (MT) bundles controls the precise localization of spindle pole body (SPB), and hence the division septum, at the onset of mitosis. 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 simultaneous control of reliability and robustness is required to minimize septum positioning error 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 the maximum fidelity of WT. Using this, we perform a sensitivity analysis of the parameters that control nuclear centering.