Long-Range Repulsion Between Chromosomes in Mammalian Oocyte Spindles

Kavli Affiliate: Daniel J. Needleman

| First 5 Authors: Colm P Kelleher, Yash Rana, Daniel J Needleman, ,

| Summary:

During eukaryotic cell division, a microtubule-based structure called the
spindle exerts forces on chromosomes, thereby organizing and segregating them
Extensive work demonstrates that the forces acting parallel to the spindle
axis, including those responsible for separating sister chromatids, are
generated by microtubule polymerization and depolymerization, and
molecular-motors. In contrast, little is known about the forces acting
perpendicular to the spindle axis, which determine the configuration of
chromosomes at the metaphase plate, and thus impact nuclear localization and
rates of segregation errors. Here, we use quantitative live-cell microscopy to
show that metaphase chromosomes are spatially anti-correlated in mouse oocyte
spindles, indicating the existence of hitherto unknown long-range forces acting
perpendicular to the spindle axis. We explain this observation by first
demonstrating that the spindle’s microtubule network behaves as a nematic
liquid crystal, and then arguing that deformation of the nematic field around
embedded chromosomes causes long-range repulsion between them. 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 organization in large spindles.

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