Insights into the Assembly of Peptides Catalyzed by Polysaccharides

Nucleation is a critical step that determines the assembly pathway and the structure and functions of the peptide assemblies. However, the dynamic evolution of interactions between nucleating agents and peptides, as well as between peptides themselves during the nucleation process, remains elusive. Herein, we show that the heterogeneous nucleating agent carboxymethylcellulose (CMC) can promote the nucleation of Aβ_16-20 (KF) peptide. The Förster resonance energy transfer (FRET) technology was used to unveil the interaction dynamics between the CMC and KF peptide. Initially, CMC enriches KF monomers through weak nondirectional electrostatic interactions. The electrostatic screening reduces the electrostatic repulsion between KF molecules. Subsequently, KF-KF interactions become dominant, leading to the dissociation of KF from the CMC and nucleation. By adjustment of the adding time, dosage, size, and active sites of CMC, the assembly kinetics of KF can be effectively controlled. This study helps gain a deep understanding of the early heterogeneous nucleation process of peptide assembly and provides valuable guidance for the rational design of efficient nucleating agents for peptide assembly toward functional materials.