Water is synonymous with life, and accordingly, proteins have evolved to utilise the ensemble of forces that arise in aqueous environments. This in turn drives protein folding, modulates dynamical behaviour, and provides a continuum for substrate and product mass transport. Although some proteins can retain some activity when dispersed in anhydrous solvents, we have demonstrated that completely solvent-free (molten) protein liquids can be produced through the rational design of a compact polymer surfactant corona. Here, the electrostatically-grafted surfactant molecules extend the range of the attractive intermolecular interactionsto a length scale that is commensurate with melting, and the resulting anhydrous biofluids still exhibit protein folding¹, dynamics² and function³.

Our recent development of a new class of functional solvent-free liquid enzymes⁴ raises questions concerning the pervasiveness of water in enzymolysis and whether biocatalysis can be undertaken in the absence of a protein hydration shell. Significantly, we were able to demonstrate lipase-mediated catalysis with neat reagent-based solvents and lyophilized powders using solvent-free melts of lipase-polymer surfactant nano-conjugates. Here, desiccated substrates in liquid (p-nitrophenyl butyrate) or solid (p-nitrophenyl palmitate) form were directly mixed or solubilized, respectively, into the biofluids, and the efficiency of product formation increased as the temperature was raised to 150 °C. These properties, which are unprecedented in protein-based nanomaterials, demonstrate that the polymer surfactant corona surrounding the enzyme not only provides access to a prohibited liquid phase, but also produces an interconnected continuum for substrate and product mobility between the active sites.