Key Intermediate Nanostructures in the Self-Assembly of Amphiphilic Polypeptoids Revealed by Cryo-TEM

作者：Yen Jea Lee, Xubo Luo, M. Seidler, Tianyi Yu, David Prendergast, Ronald N. Zuckermann, Nitash P. Balsara, Brooks A. Abel, Xi Jiang · 发表于：Macromolecules · 年份：2025 · DOI：10.1021/acs.macromol.5c00120 · 被引用次数：5 · 研究领域：Supramolecular Self-Assembly in Materials、Force Microscopy Techniques and Applications、Nanoparticle-Based Drug Delivery

Amphiphilic copolypeptoids are known to form a variety of nanostructures (fibers, tubes, sheets, etc.), but the assembly mechanisms and key intermediates remain underexplored. This study investigates the intermediate structures formed during the early stages of self-assembly in diblock copolypeptoids using cryo-transmission electron microscopy (cryo-TEM). We focused on two diblock copolypeptoids, one with a free N -terminus and the other with a capped N -terminus, which ultimately form less-ordered nanofibers and well-ordered nanosheets, respectively. Through cryo-TEM imaging of vitrified solutions at various time points during the self-assembly process, the study identified micelles and vesicles as key intermediate structures. Notably, the formation of vesicles as intermediates is unusual in crystallization-driven self-assembly and suggests a unique pathway in polypeptoid self-assembly. The study provides direct imaging evidence of key intermediates in polypeptoid self-assembly, advancing the understanding of their self-assembly mechanisms.