Genetically Encoded Sterol-Modification of a Synthetic Intrinsically Disordered Protein Drives Its Self-Assembly Into Diverse Morphologies

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 conjugation 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 STaMPs exhibit sterol-dependent self-assembly behavior, ranging from predominantly monomeric random coils for the most hydrophilic sterols to spherical micelles for the most hydrophobic sterols. Furthermore, the sterols modify the typical LCST behavior of ELPs in a predictable fashion depending on the hydrophobicity of the sterol appended.