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Before cell division, two identical copies of chromosomes are pulled apart bymicrotubule (MT) filaments that approach the chromosomes from the oppositepoles a mitotic spindle. Connection between the MTs and the chromosomes aremediated by a molecular complex called kinetochore. An externally appliedtension can lead to detachment of the MTs from the kinetochore; the meanlifetime of such an attachment is essentially a mean first-passage time. Intheir in-vitro pioneering single-kinetochore experiments, Akiyoshi et al.(Nature 468, 576 (2010)), observed that the mean lifetimes of reconstitutedMT-kinetochore attachments vary non-monotonically with increasing tension. Thecounter-intuitive stabilization of the attachments by small load forces wasinterpreted in terms of a catch-bond-like mechanism based on a phenomenological2-state kinetic model. Here we develop the first detailed microscopic model forstudying the dependence of the lifetime of the MT-kinetochore attachment on (a)the structure, (b) energetics, and (c) kinetics of the coupling. Thecatch-bond-like mechanism emerges naturally from this model. Moreover,in-silico experiments on this model reveal further interesting phenomena,arising from the subtle effects of competing sub-processes, which are likely tomotivate new experiments in this emerging area of single-particle biophysics.

A theoretical model for attachment lifetimes of kinetochore-microtubules: Mechano-kinetic "catch-bond" mechanism for error-correction