SH-SY5Y human neuroblastoma cells are commonly used as neuronal models. Here, we examined different aspects of SH-SY5Y cell differentiation. Various differentiation protocols have been proposed previously, including treatments with retinoic acid, brain-derived neurotrophic factor (BDNF), cholesterol and oestradiol. We examined undifferentiated SH-SY5Y cells (UNDIFF); cells differentiated by the treatment with retinoic acid (RA); retinoic acid + BDNF (RB); and retinoic acid + BDNF + cholesterol + oestradiol (RBCE). We performed whole-cell patch-clamp recordings from these cells and nanomechanically characterised them by using atomic force microscopy (AFM). Our results indicated that Na⁺ currents become most pronounced in the differentiated RB cells, whereas UNDIFF SH-SY5Y cells had significantly larger K⁺ currents, which is a characteristic feature of cancer cells. AFM observations of these two groups showed that Young’s moduli of SH-SY5Y cells increased threefold with differentiation. Furthermore, we showed a direct relationship between Na⁺ channel activity and elasticity in these cells. We conclude that SH-SY5Y human neuroblastoma cells should be used as a neuronal model only when they are differentiated by the treatment with retinoic acid and BDNF.

SH-SY5Y人神经母细胞瘤细胞通常用作神经元模型。在这里，我们检查了SH-SY5Y细胞分化的不同方面。先前已经提出了各种分化方案，包括用视黄酸，脑源性神经营养因子（BDNF），胆固醇和雌二醇治疗。我们检查了未分化的SH-SY5Y细胞（UNDIFF）；通过视黄酸（RA）处理分化的细胞；视黄酸+ BDNF（RB）; 和视黄酸+ BDNF +胆固醇+雌二醇（RBCE）。我们从这些细胞进行了全细胞膜片钳记录，并通过使用原子力显微镜（AFM）对其进行了纳米机械表征。我们的结果表明，Na ⁺电流在分化的RB细胞中最明显，而UNDIFF SH-SY5Y细胞的K明显更大⁺电流，这是癌细胞的特征。原子力显微镜对这两组的观察表明，SH-SY5Y细胞的杨氏模量随着分化而增加了三倍。此外，我们显示了这些细胞中Na ⁺通道活性与弹性之间的直接关系。我们得出的结论是，仅当SH-SY5Y人成神经细胞瘤细胞通过视黄酸和BDNF处理而分化时，才应将其用作神经元模型。