Interfacial effect on the ability of peptide-modified gold nanoclusters to inhibit hIAPP fibrillation and cytotoxicity

Abstract

Deposit of amyloid peptides in the cells is related to various amyloidosis diseases. A variety of nanomaterials have been developed to resist amyloid deposit. Most of the research on the inhibition of nanomaterials against amyloid aggregation are undertaken in solution, while the membranes that may mediate fibrillar aggregation and affect interaction of inhibitors with amyloid peptides in biotic environment are little taken into account. In this study, we synthesized three kinds of gold nanoclusters modified with cysteine (C@AuNCs), glutathione (GSH@AuNCs) and a peptide derived from the core region of hIAPP fibrillation (C-HL-8P@AuNCs), and investigated their inhibitory activities against hIAPP fibrillation in the absence and presence of lipid vesicles (POPC/POPG 4:1 LUVs) by the experiments of ThT fluorescence kinetics, AFM and CD. We also explored the inhibitions of hIAPP-induced membrane damage and cytotoxicity by peptide@AuNCs using fluorescent dye leakage and cell viability assays. Our study revealed that the inhibitory efficiency of these peptide@AuNCs against hIAPP fibrillation follows C-HL-8P@AuNCs≅GSH@AuNCs>C@AuNCs in lipid-free solution and C-HL-8P@AuNCs≫GSH@AuNCs>C@AuNCs in lipid membrane environment. Compared with the results obtained in lipid-free solution, the inhibitions of hIAPP fibrillation observed in lipid membrane environment were more associated with the inhibitions of hIAPP-induced damages of lipid vesicles and INS-1 cells (C-HL-8P@AuNCs≫GSH@AuNCs>C@AuNCs). An additional hydrophobic interaction with the homologous core region of hIAPP, which is only provided by C-HL-8P@AuNCs and largely suppressed in lipid-free solution, enhanced in the membrane environment and therefore made C-HL-8P@AuNCs much more powerful than GSH@AuNCs and C@AuNCs in the inhibitions of hIAPP fibrillation and cytotoxicity.