Jose Natali, David Quan and Kris Skotheim
Microtubules are important for the cellular processes of internal transport, motility and division, but very little is known for sure about how interactions on the molecular level help determine their macroscopic behavior. By developing a mechanical model of a microtubule and assuming only interactions that are widely accepted, we hope to reproduce observable microtubule structure and behavior. The leading theory for a mechanism of hydrolysis used to be that the probability of hydrolysis is completely independent of the state of nearby dimers. This was largely disproved by experiments showing time between catastrophe and dilution to be independent of the rate of growth prior to dilution. By diluting the concentration of dimers in our universe, we simulated catastrophe with this hydrolysis scheme and two others that possibly explain these experimental results. We found that if the probability of microtubule-bound dimers undergoing hydrolysis depends on the hydrolysis state of nearby dimers we could reproduce expected structures associated with growth and catastrophe. If, as suggested by E Nogales (1999), hydrolysis is catalyzed by the addition of an alpha-subunit on top of the beta subunit in the dimer below, our model displayed a GTP cap one or two dimers deep. This was not enough to prevent protofilament curling, but only when we considered detachment of oligomers did we actually observe catastrophe.
The movies below were generated using our simulation to investigate microtubule dynamics. Click on the thumbnail to see the full movie.
Movie showing splaying and curling of filaments |
Movie showing depolymerization of microtubule |
