Charge modifications of graphene oxide enhance the inhibitory effect on insulin amyloid fibrillation based on electrostatic interactions

Abstract

Graphene oxide (GO) is a biocompatible nanomaterial that has an inhibitory effect on insulin amyloid fibrillation. In order to enhance the inhibitory effect of GO and explore the rules of electrostatic interactions on the inhibitory effect, carboxyl group, PEI and PEG were coupled to the GO nanoplatelet surface to prepare inhibitors of different surface electrical properties. The effects of surface electrical properties of inhibitors on insulin fibrillation were investigated. The results showed that GO, carboxyl group modified GO (GO-COOH), PEI modified GO (GO-PEI), and PEG modified GO (GO-PEG) inhibited insulin fibrillation in a dose-dependent manner. Compared with GO, positive charge-modified GO-PEI and negative charge-modified GO-COOH enhanced the inhibitory effect, while uncharged polymer-modified GO-PEG weakened the inhibitory effect. The inhibitory effect of the inhibitors increased with the increase of surface charge density. The difference in inhibitory effect between GO-PEI and GO-COOH was due to the different electrostatic interactions between inhibitors and insulin, and the different inhibition mechanisms. In addition, inhibitors mainly interact with insulin during the nucleation phase to hinder insulin fibrillation. The charge modifications of graphene oxide enhanced the inhibitory effect on insulin fibrillation based on electrostatic interactions, which will provide new thoughts for the development of anti-amyloid fibrillation drugs.