Short-term interactions between microtubules and actin filaments underlie long-term behaviour in neuronal growth...

We present two new computational models of microtubule dynamics in the neuronal growth cone. These extend previous models of microtubule dynamics, which have neglected the effect of microtubule interactions with one another and with F-actin in the growth cone. Ultimately, these interactions determine whether the nerve cell makes the right target connections. In the first model, analysis of the effect of microtubule bundling on axonal elongation shows that small interaction effects between individual microtubules can be amplified within the microtubule bundle to significantly alter the rate of axonal growth. The second model concerns the effect of interactions between microtubules and F-actin on growth-cone turning. The model simulates microtubule invasion into the growth cone after contact with a target cell. Results suggest that microtubules do not randomly invade the growth cone, which supports the recent view that microtubules play a more active role in pathfinding than previously expected. Our results indicate that microtubule interactions with F-actin and with other microtubules play a fundamental role in axonal elongation and growth-cone turning.