Facile fabrication of high-definition hierarchical wrinkle structures for investigating the geometry-sensitive fate commitment of human neural stem cells.

Since neural stem cells (NSCs) interact with biophysical cues from their niche during development, it is important to understand the biomolecular mechanism how the NSCs process these biophysical cues to regulate their behaviors. In particular, anisotropic geometric cues in micro-/nanoscale have been utilized to investigate the biophysical effect of the structure on NSCs behaviors. Here, a series of new nanoscale anisotropic wrinkle structures with the wide range of wavelength scales (from 50 nm to 37 μm) was developed to demonstrate the effect of the anisotropic nanostructure on the fate commitment of NSCs. Intriguingly, two distinct characteristic length scales promoted the neurogenesis. Each wavelength scale showed a striking variation in terms of dependency on the directionality of structures, suggesting the existence of at least two different ways in processing of anisotropic geometries for neurogenesis. Furthermore, combined effect of the two distinctive length scales was observed by employing hierarchical multiscale wrinkle structures with two characteristic neurogenesis-promoting wavelengths. Taken together, the wrinkle structure system developed in this study can serve as an effective platform to advance the understanding of how cells sense anisotropic geometries for their specific cellular behaviors. Furthermore, this could provide clues for improving nerve regeneration system of stem cell therapies.