Soft surfaces induce neural differentiation via the neuron restrictive silencer factor

The physical and mechanical environment influence the differentiation and culture of stem cells. Early research in this field showed that mesenchymal stem cells (MSCs) adopt preferential lineages when cultured on surfaces of varying stiffness. Culture on very soft surfaces promoted neural differentiation. This effect has been observed in mesenchymal and embryonic stem cells and was shown to increase development of neural stem cells. However, providing further information on the molecular characterization of this phenomenon could help to guide the development of materials that enhance neural differentiation. Previously, our laboratory showed that chemical cues, forskolin and IBMX, induced neural differentiation of MSCs by downregulating the Neuron Restrictive Silencer Factor, leading to de-repression of neural gene expression. We sought to determine if the mechanism whereby soft surfaces induce neural differentiation could also involve NRSF function. We show that MSCs cultured on soft polydimethylsiloxane (PDMS) surfaces have reduced expression of NRSF as well as altered localization of NRSF. This suggests the modulation of transcription factors by surface substrate could be capi-talized upon in designing materials for neural cell culture.