Insights into the\nAssembly of Peptides Catalyzed by\nPolysaccharides

Nucleation is a critical step that determines the assembly\npathway\nand the structure and functions of the peptide assemblies. However,\nthe dynamic evolution of interactions between nucleating agents and\npeptides, as well as between peptides themselves during the nucleation\nprocess, remains elusive. Herein, we show that the heterogeneous nucleating\nagent carboxymethylcellulose (CMC) can promote the nucleation of Aβ<sub>16–20</sub> (KF) peptide. The Förster resonance energy\ntransfer (FRET) technology was used to unveil the interaction dynamics\nbetween the CMC and KF peptide. Initially, CMC enriches KF monomers\nthrough weak nondirectional electrostatic interactions. The electrostatic\nscreening reduces the electrostatic repulsion between KF molecules.\nSubsequently, KF–KF interactions become dominant, leading to\nthe dissociation of KF from the CMC and nucleation. By adjustment\nof the adding time, dosage, size, and active sites of CMC, the assembly\nkinetics of KF can be effectively controlled. This study helps gain\na deep understanding of the early heterogeneous nucleation process\nof peptide assembly and provides valuable guidance for the rational\ndesign of efficient nucleating agents for peptide assembly toward\nfunctional materials.