Engineering Nanointerfaces of Au<sub>25</sub> Clusters for Chaperone-Mediated Peptide Amyloidosis
Guanbin Gao, Xinglin Liu, Zhenhua Gu, Qingxue Mu, Guowei Zhu, Ting Zhang, Cheng Zhang, Ling Zhou, Lei Shen, Taolei Sun
Abstract
Synthetic nanomaterials possessing biomolecular-chaperone functions are good candidates for modulating physicochemical interactions in many bioapplications. Despite extensive research, no general principle to engineer nanomaterial surfaces is available to precisely manipulate biomolecular conformations and behaviors, greatly limiting attempts to develop high-performance nanochaperone materials. Here, we demonstrate that, by quantifying the length (−SCxR±, x = 3–11) and charges (R– = −COO–, R+ = −NH3+) of ligands on Au25 gold nanochaperones (AuNCs), simulating binding sites and affinities of amyloid-like peptides with AuNCs, and probing peptide folding and fibrillation in the presence of AuNCs, it is possible to precisely manipulate the peptides’ conformations and, thus, their amyloidosis via customizing AuNCs nanointerfaces. We show that intermediate-length liganded AuNCs with a specific charge chaperone peptides’ native conformations and thus inhibit their fibrillation, while other types of AuNCs destabilize peptides and promote their fibrillation. We offer a microscopic molecular insight into peptide identity on AuNCs and provide a guideline in customizing nanochaperones via manipulating their nanointerfaces.