Chromosome oscillation is the back-and-forth movement of chromosomes, specifically paired kinetochores, along the mitotic spindle axis during metaphase. This oscillation arises from a dynamic balance of forces within the spindle, generated through complex microtubule-chromosome interactions. These microtubule-mediated forces are regulated by microtubule dynamics, motor proteins, and tension sensing at the centromere—the constricted chromosomal region linking sister chromatids. Understanding the mechanics of chromosome oscillation is important because it provides a window into the otherwise invisible forces at work within the spindle. While some past studies have examined the contribution of various forces driving chromosome oscillation, the specific role of centromeric stiffness in shaping oscillation remains elusive. A centromere appears to act as a spring, transmitting biomechanical signals during mitosis. Experimentally, we observed that a valproic acid (VPA)-induced softer centromere resulted in oscillations with slightly longer cycle period and smaller amplitudes. Additionally, kinetochore-microtubule stability increased when centromere stiffness was either increased or decreased. Directly measuring and tuning forces in cells is challenging, but mathematical models offer a powerful means to complement experiments. To elucidate how centromere stiffness influences the mechanics underlying chromosome oscillation, we developed a parsimonious agent-based model of kinetochore-microtubule dynamics that reverse-engineers chromosome oscillation. Our model provides a mechanistic explanation for the experimentally observed oscillation features upon altering centromeric stiffness. Furthermore, the model suggests the most plausible mechanisms by which centromere stiffness may regulate kinetochore-microtubule attachment stability.
Chatterjee et al. (2026) studied this question.