Genetically encoded sterol-modification of a synthetic intrinsically disordered protein leads to diverse self-assembly behavior

Post translational modifications (PTMs) of proteins are used by natural systems to expand beyond the 20 canonical amino acids. The variation introduced at the sequence level by PTMs after expression leads to changes in both the structure and function of proteins. PTMs expand the chemical repertoire from which new biomaterials can be constructed. Inspired by the post-translational addition of cholesterol to proteins, we have synthesized five new hybrid lipid-protein biomaterials called Sterol modified polypeptides (STaMPs). These STaMPs consist of an elastin like polypeptide (ELP) conjugated to a sterol, namely coprostanol, epicoprostanol, androstanol, galeterone, or dehydroepiandrosterone. We show that the STaMPs form self-assembled nanostructures such as spherical and cylindrical micelles, and vesicles. Furthermore, the sterols modify the typical LCST behavior of ELPs in a predictable fashion depending on the hydrophobicity of the sterol appended. STaMPs could expand the possibilities for drug delivery by enabling the physical encapsulation of hydrophobic drugs, increasing the solubility and half-life of sterol-based chemotherapeutics, and forming thermosensitive drug depots.