Long-Range Repulsion Between Chromosomes in Mammalian Oocyte Spindles

During eukaryotic cell division, a microtubule-based structure called the spindle organizes and segregates chromosomes. According to the best-studied models of spindle force generation, including microtubule depolymerization and molecular-motor-driven sliding, forces are generated by nanometer-scale molecular processes and then transmitted over distances of microns by rigid microtubules lying parallel to the spindle long axis. While many important questions about force generation, regulation, and transmission remain unsolved, these mechanisms can in principle explain chromosome motion along the spindle axis, including congression to the metaphase plate (i.e. the spindle mid-plane), and the separation of sister chromatids in anaphase. However, they cannot account for forces in the perpendicular direction, and it remains unclear which physical principles determine the chromosome configuration within the metaphase plate. Here, we use quantitative live-cell microscopy to show that metaphase chromosomes are spatially anti-correlated in mouse oocyte spindles, consistent with the existence of hitherto unknown long-range forces acting perpendicular to microtubules. We demonstrate that a simple continuum model can account for this observation, as well as several other measurements of the structure and dynamics of the microtubule network itself. In this model, the spindle is treated as an active nematic liquid crystal droplet, the orientation of microtubules throughout the spindle is determined by nematic elasticity, condensed chromosomes act like micron-scale inclusions in a continuous nematic phase, and long- range repulsive forces arise due to deformation of the nematic field around embedded chromosomes. Our work highlights the surprising relevance of materials physics in understanding the structure, dynamics, and mechanics of cellular structures, and presents a novel and potentially generic mode of chromosome self-organization in large spindles.