- Stem cells sense and respond to the stiffness of the surface on which they adhere. Many studies showed that surface elasticity could control cell proliferation and cell differentiation through biochemical pathways. Adipose-derived stem cells (ADSCs) are multipotent and can differentiate along the adipocyte, chondrocyte, myocyte, neuronal, and osteoblast lineages which can be used as a source of stem cells for cell therapy in the future. We hypothesized that ADSCs could differentiate to neurons in response to the softness of the surface on which they adhere. The aim of this study were the use of soft surface to induce neuronal differentiation of ADSCs then neuronal gene expression was observed by Real- Time PCR and to study critical regulatory roles of redox proteins in surface elasticitymediated signal transduction and outgrowth of ADSCs. Photolithographic technique was used to control degree of cross-linking in the gelatinous hydrogel. This kind of hydrogel could mimic a mechanical property of brain tissue. Gelatinous hydrogels with surface elasticity ~ 1-5 kPa were used as biomaterial scaffolds to induce neuronal differentiation of ADSCs. ADSCs were cultured on soft surface for 1-2 weeks and the expressions of class III beta-tubulin and redox genes were detected by RT-PCR. It was found that class III betatubulin gene was up-regulated in ADSCs cultured on hydrogel when compared with ADSCs cultured on tissue culture polystyrene. This result indicated that neuronal differentiation of stem cells culture on hydrogel could be achived without addition of any supplement. This study indicated that neural differentiation is involved with change of redox protein expression. Redox proteins such as thioredoxin (TRX) and superoxide dismutase (SOD) have dual roles in a variety of biological processes including cytoprotection and the activation of transcription factors. The expression of Trx 1, SOD 1 and PRX2 genes were up-regulated in stem cells cultured on soft surface when compared with stem cells cultured on tissue culture polystyrene. In conclusion, neural differentiation of stem cells culture on soft matrix is involved with change in expression of redox proteins.