Self-Assembly of pH-Responsive Star-Shaped Amphiphilic Polypeptides Based on l‑Lysine and l‑Leucine

Polypeptides are attractive, renewable, and biocompatible materials for broad potential biomedical, pharmaceutical, and regenerative medicine applications. In this study, star-shaped 3-arm amphiphilic polypeptides with self-assembly characteristics were synthesized by ring-opening polymerization (ROP) of N-carboxyanhydride (NCA), incorporating l-leucine and l-lysine to form a core-shell structure. These polymers were thoroughly characterized through various techniques, revealing that their rheological behavior and self-assembly are influenced by factors such as the length of the star-shaped arms, the proportion of hydrophobic amino acids, and the surrounding pH. The synthesized polypeptides can self-assemble into five distinct secondary structures, mimicking natural proteins. Our findings evidence that the design of the block size of the hydrophilic l-lysine core and hydrophobic l-leucine shell shapes the ability to form a physical hydrogel, exhibiting shear-thinning rheological characteristics and a rapid mechanical response. The internal microstructure of the hydrogel is based on a supramolecular self-assembly structure consisting of highly connected nanofibrils.