2022/04/09 by Pooja K Suresh, Suresh, Pooja, Vahe Galstyan +5
Biochemistry, Genetics and Molecular Biology · Engineering · #Advanced Materials and Mechanics #Biological Physics (physics.bio-ph) #Cell Behavior (q-bio.CB) #Cellular Mechanics and Interactions #FOS: Biological sciences #FOS: Physical sciences #Microtubule and mitosis dynamics
paper · pdf · doi:10.48550/arxiv.2204.04461
openalex publication_date 2022/04/09 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/28
During cell division, the spindle generates force to move chromosomes. In mammals, microtubule bundles called kinetochore-fibers (k-fibers) attach to and segregate chromosomes. To do so, k-fibers must be robustly anchored to the dynamic spindle. We previously developed microneedle manipulation to mechanically challenge k-fiber anchorage, and observed spatially distinct response features revealing the presence of heterogeneous anchorage (Suresh et al. 2020). How anchorage is precisely spatially regulated, and what forces are necessary and sufficient to recapitulate the k-fiber's response to force remain unclear. Here, we develop a coarse-grained k-fiber model and combine with manipulation experiments to infer underlying anchorage using shape analysis. By systematically testing different anchorage schemes, we find that forces solely at k-fiber ends are sufficient to recapitulate unmanipulated k-fiber shapes, but not manipulated ones for which lateral anchorage over a 3 μm length scale near chromosomes is also essential. Such anchorage robustly preserves k-fiber orientation near chromosomes while allowing pivoting around poles. Anchorage over a shorter length scale cannot robustly restrict pivoting near chromosomes, while anchorage throughout the spindle obstructs pivoting at poles. Together, this work reveals how spatially regulated anchorage gives rise to spatially distinct mechanics in the mammalian spindle, which we propose are key for function.