Poly(ethylene glycol) Crystallization in Multifunctional Polypeptide–Polymer Hybrids Based on Human Serum Albumin Scaffolds

We employ cationized human serum albumin as a scaffold for attaching poly(ethylene glycol) (PEG) chains at precise locations along the protein backbone. Subsequent denaturation unfolds the protein backbone, resulting in brush polymers with a well-defined, monodisperse, polypeptide backbone with PEG side chains. The defined variation of PEG chain number allows for a systematic investigation of the impact of PEGylation on the protein secondary structure, protein backbone and PEG dynamics, as well as PEG crystallization. Strikingly, PEG side chains in the polypeptide-PEG hybrids can crystallize even at low grafting density. As a result, crystallization is embedded in the hybrids, evident from the low degree of crystallinity, reduced melting temperature, and superslow spherulitic growth rates. The crystallization temperature in the hybrids approaches the homogeneous nucleation limit of PEG, only accessible via confinement (e.g., in nanopores). Our findings underscore the unique crystallization characteristics of PEG side chains in polypeptide-PEG hybrids.