An artificial chaperone serves a dual role in regulating the assembly of peptides through phase separation

Abstract

In biological systems, molecular assembly primarily relies on the assistance of molecular chaperones. Inspired by nature, strategies like ‘chaperone-assisted assembly’ and ‘catalyzed assembly’ have been proposed for the sophisticated control of molecular assembly. Nonetheless, significant challenges remain in the rational design of such systems, calling for a deep understanding of underlying principles. Herein, we demonstrate an artificial chaperone serves a dual role, that is catalyst in low dosages and inhibitor in high dosages, in regulating the supramolecular polymerization of peptides. Low dosages of carboxymethyl cellulose, as the chaperones, catalyze the assembly of Aβ_16-22 peptides into fibrils through multi-step phase separation, while high dosages trap the peptides into coacervate intermediates and therefore inhibit the fibrillation. Consequently, the quantity of chaperones does not follow the intuition that ‘more is better’ for catalyzing assembly but instead has an optimal molar ratio. Investigation reveals that the interplay and evolution of electrostatic and hydrophobic interactions are the keys to achieving these processes. This study provides insights into the multifaceted roles artificial chaperones may play in a dosage-dependent manner and enriches the toolkit for efficient and controllable construction of complex assembly systems.

Keywords

artificial chaperone / catassembly / dosage effect / peptide assembly / supramolecular polymerization

RIGHTS & PERMISSIONS

2024 2024 The Authors. Aggregate published by South China University of Technology; AIE Institute and John Wiley & Sons Australia, Ltd.