Since pheochromocytoma 12 (PC12) cells have the ability of neuronal differentiation upon nerve growth factor (NGF) treatment, they are a good model for studying the neuronal differentiation. Establishing a strong adhesion of PC12 cells to the culture substrate may increase neuronal differentiation, and the use of L-3,4-dihydroxypfienylalanine (L-DOPA), which is responsible for the adhesive property of mussel adhesive proteins (MAPs), is a feasible strategy for such strong adhesion. We hypothesized that a polydopamine-modified surface can promote PC12 cell adhesion and subsequent neuronal differentiation. We examined whether polydopamine-modified surface promotes PC12 cell adhesion, and further evaluated the neuronal differentiation of these cells. The polydopamine modification enhanced the cell adhesion and viability, and also promoted the neuronal differentiation of NGF-stimulated PC12 cells, as evidenced by the elongation of neurites and expression of neuronal differentiation markers, by increasing the activation of NGF/Trk-Rho GTPase signal pathway. Our findings will help develop an improved strategy for functionalizing biomaterial substrates for less-adhesive cells including neural cells. (C) 2012 Elsevier Inc. All rights reserved.