Biophysics of Microtubule End Coupling at the Kinetochore

The main physiological function of mitotic kinetochores is to provide durable attachment to spindle microtubules, which segregate chromosomes in order to partition them equally between the two daughter cells. Numerous kinetochore components that can bind directly to microtubules have been identified, including ATP-dependent motors and various microtubule-associated proteins with no motor activity. A major challenge facing the field is to explain chromosome motions based on the biochemical and structural properties of these individual kinetochore components and their assemblies. This chapter reviews the molecular mechanisms responsible for the motions associated with dynamic microtubule tips at the single-molecule level, as well as the activities of multimolecular ensembles called couplers. These couplers enable persistent kinetochore motion even under load, but their exact composition and structure remain unknown. Because no natural or artificial macro-machines function in an analogous manner to these molecular nano-devices, understanding their underlying biophysical mechanisms will require conceptual advances.