A Lateral Cap model of microtubule dynamic instability

Abstract

The co-existence and interconversion of growing and shrinking microtubules have been termed ‘dynamic instability’, and have been directly observed to occur under a variety of conditions in vitro and in vivo. Previous modelling was based on the concept of an extensive, fluctuating cap of tubulin-GTP to stabilise growing microtubules. A quantitative kinetic model is now presented in which only the terminal layer of the multi-start helical microtubule lattice contains tubulin-GTP molecules, comprising a ‘Lateral Cap’. In Monte Carlo numerical simulation, this model readily reproduces the decisive experimental evidence of microtubule dynamics, and predicts a co-operative mechanism for microtubule transitions. The model also suggests how differing kinetic properties at opposite ends are the result of the intrinsic polarity of the microtubule lattice, reflecting the polarity of the tubutin α/β heterodimer.