Roles of the Cytoskeletal Structure in Neurite Outgrowth

Neurite outgrowth is a process in which neurons generate further projections, which is mainly driven by interactions between cytoskeletal components including microtubules, cross-linkers, and dynein motors. Previous studies suggested that dynein motors interact with and walk on a pair of neighboring microtubules transiently linked by cross-linkers. However, it remains elusive how these molecular interactions result in neurite elongation at a cellular scale. To investigate the mechanisms of neurite elongation, we constructed an agent-based model that consists of essential cytoskeletal elements with consideration of their mechanical properties and mechanical interactions. Our extensive parametric studies demonstrated that more microtubules are beneficial for accelerating the neurite outgrowth, whereas a higher number of crosslinkers are antagonistic for the neurite outgrowth. We also found how a change in the average length and bending stiffness of microtubules varies the neurite elongation rate. In addition, we showed how microtubule dynamics, i.e., growth, shrinkage, and fragmentation of microtubules, and the surrounding actin cortex affect neurite outgrowth. Our results provide important insights into understanding how neurite outgrowth emerges from molecular interactions.