SHORT-TERM INTERACTIONS BETWEEN MICROTUBULES AND ACTIN-FILAMENTS UNDERLIE LONG-TERM BEHAVIOR IN NEURONAL GROWTH CONES

We present two new computational models of microtubule dynamics in the neuronal growth cone. These extend previous models of microtubule dyn amics, which have neglected the effect of microtubule interactions wit h one another and with F-actin in the growth cone. Ultimately, these i nteractions determine whether the nerve cell makes the right target co nnections. In the first model, analysis of the effect of microtubule b undling on axonal elongation shows that small interaction effects betw een individual microtubules can be amplified within the microtubule bu ndle to significantly alter the rate of axonal growth. The second mode l 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 tha t microtubules do not randomly invade the growth cone, which supports the recent view that microtubules play a more active role in pathfindi ng than previously expected. Our results indicate that microtubule int eractions with F-actin and with other microtubules play a fundamental role in axonal elongation and growth-cone turning.