  Microtubules (MTs) are cytoplasmic protein polymers that are essential for
fundamental cellular processes including the maintenance of cell shape,
organelle transport and formation of the mitotic spindle. Microtubule dynamic
instability is critical for these processes, but it remains poorly understood,
in part because the relationship between the structure of the MT tip and the
growth/depolymerization transitions is enigmatic. What are the functionally
significant aspects of a tip structure that is capable of promoting MT growth,
and how do changes in these characteristics cause the transition to
depolymerization (catastrophe)? Here we use computational models to investigate
the connection between cracks (laterally unbonded regions) between
protofilaments and dynamic instability. Our work indicates that it is not the
depth of the cracks per se that governs MT dynamic instability. Instead it is
whether the cracks terminate in GTP-rich or GDP-rich areas of the MT that
governs whether a particular MT tip structure is likely to grow, shrink, or
transition: the identity of the crack-terminating subunit pairs has a profound
influence on the moment-by-moment behavior of the MT.
