Biophysics of Kinetochore Microtubules in Human Mitotic Spindles

Abstract

During eukaryotic cell division, chromosomes are linked to microtubules in the spindle by a macromolecular complex called the kinetochore. Regulation of these bound kinetochore micro- tubules is crucial to ensuring accurate chromosome segregation; however, the kinetochore micro- tubule lifecycle, including recruitment to the kinetochore, growth, and detachment from the kinetochore, is not well understood. We utilized electron tomography reconstructions, live-cell light microscopy experiments and biophysical modeling to describe the lifecycle of kinetochore micro- tubules in human mitotic spindles. We then employed quantitative fluorescence microscopy and mathematical modeling to explain how kinetochore microtubules detach from the kinetochore and how erroneous kinetochore microtubules are selectively removed. This work leads to a self- organized, biophysical picture of kinetochore microtubules in mitotic human spindles connecting the molecular interaction of microtubules with the kinetochore to accurate chromosome segregation.