Abstract
Mitotic spindle, a micromachine composed of microtubules and associated proteins, plays a pivotal role in ensuring the accurate segregation of chromosomes. During spindle assembly, initially randomly distributed chromosomes are transported toward the equatorial plate and experiments suggest that several competing mechanisms can contribute to this process of chromosome congression. However, a systematic theoretical study of forces relevant to chromosome congression is still lacking. Here we show, by introducing a physical model, that length-dependent forces generated by motor proteins transport chromosomes toward the spindle equator. Passive crosslinkers, on the other hand, can generate off-centering forces that impair chromosome congression. Our mean-field approach also reveals that stable points can exist in the vicinity of spindle poles, in addition to the one in the center, and thus provides an explanation for erroneous spindles with polar chromosomes. Taken together, our study provides a comprehensive approach to understanding how different spindle components interact with each other and generate forces that drive chromosome congression.
Publisher
Cold Spring Harbor Laboratory