Multi‐Responsive Peptide‐Based Ultrathin Nanosheets Prepared by a Horizontal Monolayer Assembly

In this study, peptide-based self-assembled nanosheets with a thickness of approximately 1 nm were prepared using a hierarchical covalent physical fabrication strategy. The covalent alternating polymerization of helical peptide E3 with an azobenzene (AZO) structure yielded copolymers CoP(E3-AZO), which physically self-assembled into ultrathin nanosheets in an unanticipated two-dimensional horizontal monolayer arrangement. This special monolayer arrangement enabled the thickness of the nanosheets to be equal to the cross-sectional diameter of a single linear copolymer, which is a rare phenomenon. Molecular dynamics simulations suggested that the synergistic effect of multiple molecular interactions drives the self-assembly of CoP(E3-AZO) into nanosheets and that various methods, including phototreatment, pH adjustment, the addition of additives, and introduction of cosolvents, can alter the molecular interactions and modulate the self-assembly of CoP(E3-AZO), yielding diverse nanostructures. Remarkably, the ultrathin nanosheets selectively inhibited cancer cells at certain concentrations.