Interfacial interactions between PMMA nanoplastics and a model globular protein: towards a molecular understanding of nanoplastic-driven biological dyshomeostasis

Abstract

The ingestion of poly(methyl methacrylate) (PMMA) nanoplastics (NPs) is associated with numerous health issues. For example, PMMA exposure is hepatotoxic and reprotoxic. Exposure induces ecchymosis, haematomas, swelling, itching, erythema, hypertrophic scarring, hypersensitivity, palpable nodules, tissue necrosis, blindness and foreign body granuloma. Nevertheless, there remain knowledge gaps in our understanding of the mechanisms by which PMMA NPs, and NPs derived from other plastics, drive the sequelae to toxicological outcomes. To begin to address these gaps, we have examined the impact of PMMA NP exposure on the structure and function of biomolecular assemblies including proteins, cell lines and organisms (nematodes). Our results reveal that interactions between the PMMA NPs and the retinol transport protein β-lactoglobulin (BLG) resulted in altered Trp fluorescence signatures and perturbations in its secondary structure. Furthermore, exposure to the NPs compromised retinol binding, suggesting that the aforementioned structural changes also impacted the proteins' hydrophobic ligand-binding site and potentially compromised its physiological role involving nutrition, vision and brain development. Furthermore, PMMA NPs accelerated fibril formation in the amyloidogenic protein hen egg-white lysozyme (HEWL) suggesting that it exacerbates amyloid-forming trajectories. Ingestion of the NPs by the nematode C. elegans caused a significant decrease in the fluorescence of GFP-tagged dopaminergic neurons and compromised locomotory output, mimicking exposure to known amyloidogenic and Parkinsonian agents such as paraquat. Collectively, the findings provide insight into mechanism(s) by which PMMA NPs corrupt bimolecular structure and function, induce amyloidosis, onset neuronal injury and drive aberrant physiological and behavioral outcomes suggestive of neurotoxicity.