Cooperative modulation of neuritogenesis by PC12 cells by topography and nerve growth factor

Understanding axonal formation and contact guidance are of critical importance for the design of materials that interface with neuronal tissue. Contact guidance of neurites by topographic features is well known, but the role that topography plays in the modulation of neuritogenesis has not been addressed. To test this, we cultured PC12 cells with a range of nerve growth factor (NGF) concentrations on surfaces with ridge widths ranging from 70 to 1900 nm. We find that neuritogenesis by PC12 cells cultured with sub-optimal concentrations of NGF (25 and 5 ng/ml) is modulated by topographic feature size. The threshold for induction of neuritogenesis was markedly reduced when cells were cultured on ridges of 70 and 250 nm. In contrast, contact guidance of neurites was independent of feature size. These results suggest that the scale of topographic features can act cooperatively with NGF signaling to regulate the formation of neurites. These findings may have general relevance to differentiation processes in neurons as well as in other cell types.