Molecular Control of Interfacial Fibronectin Structure on Graphene Oxide Steers Cell Fate

The use of graphene-based materials (GBMs) for tissue-engineering applications has been growing exponentially because of the seemingly endless multifunctional and tunable physicochemical properties of graphene that can be exploited to influence cellular behavior. Despite many demonstrations wherein cell physiology has been modulated on different GBMs, a clear mechanism connecting the different physicochemical properties of GBMs to cell fate has remained elusive. In this work, we demonstrate how different GBMs can be used to bias cell fate in a multiscale study-starting from serum protein (fibronectin) adsorption and its molecular scale morphology, structure, and bioactivity and ending with stem cell response. Using heat to chemically reduce graphene oxide without changing physical properties, we show that graphene chemistry controls surface-adsorbed molecular conformation and morphology, epitope presentation, and stem cell attachment. Moreover, this subtle change in the protein structure was found to drive increased bone differentiation of stem cells, suggesting that the physicochemical properties of graphene biases cell fate by directly influencing the adsorbed protein structure and subsequent biochemical activity.