Mapping k-fiber load-bearing in the mammalian spindle reveals local anchorage that provides mechanical isolation and redundancy

Invited

Abstract

During cell division, a self-organizing microtubule-based machine called the mitotic spindle aligns and segregates chromosomes into two new cells. Forces transmitted through k-fiber microtubule bundles push and pull chromosomes to align them in the center of the cell. To oppose these forces, the spindle must robustly anchor its k-fibers, but where or how that anchorage occurs is not well-understood, nor are the mechanical properties of the k-fibers themselves. In part, this is due to the challenge of probing mechanics in live cells. To map load-bearing in the mammalian spindle across space and time, we laser ablate single k-fibers and quantify the immediate relaxation of chromosomes and surrounding microtubules and find only local load redistribution within a few microns of kinetochores. We describe a phenomenological model consistent with this behavior: dense, transient crosslinks that attach k-fibers to the spindle and bear load without limiting the timescale of spindle reorganization. We find that the microtubule crosslinker NuMA is required for wild-type levels of local load-bearing, whereas PRC1 and Eg5 are not. Local load-bearing provided by NuMA is well-suited to robust k-fiber anchorage that provides mechanical redundancy while permitting dynamic spindle rearrangements.

Authors

  • Mary Elting

    North Carolina State University