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The formation of neuron networks is a process of fundamental importance forunderstanding the development of the nervous system and for creating biomimeticdevices for tissue engineering and neural repair. The basic process thatcontrols the network formation is the growth of an axon from the cell body andits extension towards target neurons. Axonal growth is directed byenvironmental stimuli that include intercellular interactions, biochemicalcues, and the mechanical and geometrical properties of the growth substrate.Despite significant recent progress, the steering of the growing axon remainspoorly understood. In this paper, we develop a model of axonal motility, whichincorporates substrate-geometry sensing. We combine experimental data withtheoretical analysis to measure the parameters that describe axonal growth onmicropatterned surfaces: diffusion (cell motility) coefficients, speed andangular distributions, and cell-substrate interactions. Experiments performedon neurons treated with inhibitors for microtubules (Taxol) and actin filaments(Y-27632) indicate that cytoskeletal dynamics play a critical role in thesteering mechanism. Our results demonstrate that axons follow geometricalpatterns through a contact-guidance mechanism, in which geometrical patternsimpart high traction forces to the growth cone. These results have importantimplications for bioengineering novel substrates to guide neuronal growth andpromote nerve repair.

Neuronal Growth and Formation of Neuron Networks on Directional Surfaces