Synergistic effect of polystyrene nanoplastics and contaminants on the promotion of insulin fibrillation

Nanoplastics (NPs) are becoming an emerging pollutant of global concern. A potential risk of NPs is that they can serve as carriers and synergistically function with other contaminants to cause diseases. A variety of diseases such as Alzheimer’s disease are related to the generation of amyloid fibrils, and insulin is typically used as a model to study the fibrillation process. In this study, we examined the fibrillation of insulin promoted by polystyrene nanoplastics (PSNPs) alone and synergistically with organic contaminants (denoted as X, X = pyrene, bisphenol A, 2,2′,4,4′-tetrabromodiphenyl ether, 4,4′-dihydroxydiphenylmethane, or 4-nonylphenol) having different polarities using thioflavin T fluorescence assays, dynamic light scattering, and circular dichroism spectroscopy. The presence of PSNPs and small organic contaminants decreased the lag phase time (tlag) for insulin fibrillation from 54.6 h to 35-51 h and their combination (PS-X) enhanced this process (tlag = 21-30 h). Notably, the lag phase time for insulin fibrillation with PS-nonpolar contaminants, PS-weakly polar contaminants, and PS-polar contaminants is around 20.8, 26.7, and 30.1 h, respectively, indicating the synergistic effect of PS-nonpolar contaminants or PS-weakly polar contaminants was more obvious than that of PS-polar contaminants. Moreover, molecular dynamic simulation reveal the interactions between insulin and PSs or small organic contaminants are primarily driven by van der Waals forces and hydrophobic interactions. Overall, the findings of this study underscore the potentially significant environmental impact of small organic contaminants assisting NPs in promoting insulin fibrillation. Polystyrene nanoplastics and small organic contaminants synergistically promoted the fibrillation of insulin at the nucleation step by allowing insulin to more easily approach PSNPs and enhancing the conformational transition. [Display omitted] •The combination of PS and contaminants shortened the lag time of nucleation and significantly promoted insulin aggregation.•Non-polar and weakly polar organics perform more significantly in promoting insulin aggregation.•The interactions between insulin and PSs or PS-Xs are primarily driven by van der Waals forces and hydrophobic interactions.•PSs and PS-Xs enhance the conformational transition of insulin and promote the formation of fibril nuclei.