BPS2026 – Mammalian metaphase kinetochores are deformable, elastic materials dependent on condensin for structural robustness and functional integrity

The mammalian kinetochore connects chromosomes to dynamic spindle microtubules. To remain attached, it must maintain its structural integrity under force, but to what extent and how it does so remain unclear. Under metaphase spindle forces, we find using super resolution microscopy that inner (CENP-A) and outer (Hec1) kinetochores under correlated, large-scale (1 μm) deformations along the force axis, suggesting dynamic, relative sliding of parallel protein linkages. Kinetochore shape changes can asymmetric, with centromere-facing “tails” correlating with erroneous attachment geometries. Applying microneedle pulling forces, we demonstrate that kinetochores are elastic, stretching under force and rapidly relaxing afterward. Finally, we show that SMC2 depletion results in more variable kinetochore deformations, despite maintained elasticity, and in reduced microtubule attachment stability. Thus, the kinetochore is structurally highly dynamic and requires a stiff centromere base for structural maintenance and function under force. We propose a model whereby individual protein linkages are stiff yet global kinetochore structure flexible to accommodate different attachment geometries and forces while maintaining function.