Modeling the Axon as an Active Partner with the Growth Cone in Axonal Elongation

Abstract

Forces generated by the growth cone are vital for the proper development of the axon and thus brain function. Although recent experiments show that forces are generated along the axon, it is unknown whether the axon plays a direct role in controlling growth cone advance. Here, we use analytic and finite element modeling of microtubule dynamics and the activity of the molecular motors myosin and dynein to investigate mechanical force balance along the length of the axon and its effects on axonal outgrowth. Our modeling indicates that the paradoxical effects of stabilizing microtubules and the consequences of microtubule disassembly on axonal outgrowth can be explained by changes in the passive and active mechanical properties of axons. Our findings suggest that a full understanding of growth cone motility requires a consideration of the mechanical contributions of the axon. Our study not only has potential applications during neurodevelopment but might also help identify strategies to manipulate and promote axonal regrowth to treat neurodegeneration.