Reversible transformation of peptide assembly between densified-polysarcosine-driven kinetically and helix-orientation-driven thermodynamically stable morphologies

Abstract

Stimuli-responsive transformable biomaterials development can be manipulated practically by fine-tuning the built-in molecular design of their structural segments. Here, we demonstrate a peptide assembly by the bola-type amphiphilic polypeptide, glycolic acid-polysarcosine (PSar)₁₃-b-(L-Leu-Aib)₆-b-PSar₁₃-glycolic acid (S₁₃L₁₂S₁₃), which shows morphological transformations between hydrophilic chain-driven and hydrophobic unit-driven morphologies. The hydrophobic α-helical unit (L-Leu-Aib)₆ precisely controls packing in the hydrophobic layer of the assembly and induces tubule formation. The densified, hydrophilic PSar chain on the assembly surface becomes slightly more hydrophobic as the temperature increases above 70 °C, starting to disturb the helix–helix interaction-driven formation of tubules. As a result, the S₁₃L₁₂S₁₃ peptide assembly undergoes a reversible vesicle–nanotube transformation following a time course at room temperature and a heat treatment above 80 °C. Using membrane fluidity analysis with DPH and TMA-DPH and evaluating the environment surrounding the PSar side chain with NMR, we clarify that the vesicle was in a kinetically stable state driven by the dehydrated PSar chain, while the nanotube was in a thermodynamically stable state.