Interplay between long- and short-range interactions drives neuritogenesis on stiff surfaces.

Substrate factors such as surface energy distribution can affect cell functions, such as neuronal differentiation of PC12 cells. However, the surface effects that trigger such cell responses need to be clarified and analyzed. Here we show that the total surface tension is not a critical parameter. Self-assembled monolayers of alkylsiloxanes on glass were used as culture substrates. By changing the nanoscale structure and ordering of the monolayer, we designed surfaces with a range of dispersive (γ(d) ) and nondispersive (γ(nd) ) potentials, but with a similar value for total free-energy (50 ≤ γ(d) + γ(nd) ≤ 55 mN m⁻¹). When seeded on surfaces displaying γ(d) /γ(nd) ≤ 3.7, PC12 cells underwent low level of neuritogenesis. On surfaces exhibiting γ(d) /γ(nd) ≥ 5.4, neurite outgrowth was greatly enhanced and apparent by only 24 h of culture in absence of nerve growth-factor treatment. These data indicate how the spatial distribution of surface potentials may control neuritogenesis, thus providing a new criterion to address nerve regeneration issues on rigid biocompatible surfaces.