Figure 6. Model of neurite guidance in response to nanotopographical cues.

(A) Line substrate, unaligned growth cone. Filopodia scan the line substrate through lateral scanning and protrusion/retraction events. Only few filopodia align on the lines and thus almost all filopodia sense only discrete adhesion points to the ECM. (B) Line substrate, aligned growth cone. Through stochastic sensing, multiple filopodia have aligned on the line substrate and have assembled an F-actin rich cytoskeleton that stabilizes them. On the distal part of the growth cone, non-aligned, unstable filopodia continue to operate, suggesting a crosstalk between both filopodia populations. This stabilizes the growth cone leading to steady neurite outgrowth. (C) Plain substrate. Unrestricted access to ECM leads to a large amount of long filopodia, none of which can be stabilized by a robust F-actin cytoskeleton. This is accompanied with a high frequency of neurite collapse events.