Polystyrene nanoplastic exposure promotes amyloid misfolding and metabolic impairment at sublethal doses. A subcellular infrared imaging study

ABSTRACT Microplastics and nanoplastics (MNPs) are ubiquitous environmental pollutants with increasing implications for human health. While their presence in human tissues is established, the molecular mechanisms driving their potential neurotoxicity remain unclear. This study investigates the impact of polystyrene (PS) on amyloid protein misfolding and cellular metabolism using Optical Photothermal Infrared (O-PTIR) spectroscopy, a label-free, sub-diffraction imaging technique. Our results reveal that PS exposure promotes pathological protein misfolding, specifically increasing β-sheet-rich conformations, and disrupts metabolic homeostasis at sub-lethal doses. These suggest that the microplastic surface acts as a catalytic scaffold for amyloid aggregation, driving cellular dysfunction prior to acute toxicity. This identifies a plausible molecular pathway by which environmental MNP pollution contributes to the risk and progression of neurodegenerative diseases, highlighting the need for risk assessments that look beyond simple cell survival.