Topographic cues of nano-scale height direct neuronal growth pattern

We study the role of nano-scale cues in controlling neuronal growth. We use photolithography to fabricate substrates with repeatable line-pattern ridges of nano-scale heights. We find that neuronal processes, which are of micron size, have strong interactions with ridges even as low as 10 nm. The interaction between the neuronal process and the ridge leads to a deflection of growth direction and a preferred alignment with the ridges. The interaction strength clearly depends on the ridges' height. For 25 nm ridges approximately half of the neuronal processes are modified, while at 100 nm the majority of neurites change their original growth direction post interaction. In addition, the effect on growth correlates with the incoming angle between the neuronal process and the ridge. We underline the adhesion as a key mechanism in directing neuronal growth. Our study highlights the sensitivity of growing neurites to nano-scale cues thus opens a new avenue of research for pre-designed neuronal growth and circuitry.