Molecular control of interfacial protein structure on graphene-based substrates steers cell fate

The use of graphene-based materials (GBMs) for tissue-engineering applications is growing exponentially due to the seemingly endless multi-functional and tunable physicochemical properties of graphene, which can be exploited to influence cellular behaviours. Despite many demonstrations wherein cell physiology can be modulated on GBMs, a clear mechanism connecting the different physicochemical properties of different GBMs to cell fate has remained elusive. In this work, we demonstrate how different GBMs can be used to cell fate in a multi-scale study - starting from serum protein (Fibronectin) adsorption to molecular scale morphology, structure and bioactivity, and finally ending with stem cell response. By changing the surface chemistry of graphene substrates with only heating, we show that molecular conformation and morphology of surface adsorbed fibronectin controls epitope presentation, integrin binding, and stem cell attachment. Moreover, this subtle change in protein structure is found to drive increased bone differentiation of cells, suggesting that physicochemical properties of graphene substrates exert cell control by influencing adsorbed protein structure.