Polystyrene and polyethylene perturb the structure of membrane: An experimental and computational study

There are various types and mixtures of nanoplastics (NPs) that are ubiquitous in the environment. Nevertheless, it remains a challenge to investigate the membrane effects and in vivo processes of mixtures of NPs due to their compositional complexity. In the present study, a framework combining cell assays, molecular dynamics (MD) simulations, and toxicogenomic network analysis was implemented to elucidate the differential effects of polystyrene (PS), polyethylene (PE), and the PS-PE mixture on cell membrane integrity. The cellular experiments indicated that PS, PE, and the PS-PE mixture could induce leakage of intracellular substances across the cell membrane, thereby demonstrating membrane damage. Molecular dynamics simulations revealed that these NPs could surmount energy barriers to infiltrate lipid membranes, leading to the formation of membrane pores. Notably, the PS-PE mixture showed a stronger effect than the single component. As evidenced by both cellular experiments and MD simulations, this phenomenon might be resulted from the elevated affinity of the PS-PE mixture for the lipid bilayer. The characteristic enhanced its propensity to engage with membrane structures, thereby inducing more pronounced disruption of membrane integrity. The analysis of biological networks underscored metabolic disorders and oxidative stress as key pathways for hepatotoxicity induced by NPs, elucidating the membrane damage and hepatotoxic mechanisms of NP mixtures. The study established a critical framework for assessing health risks of diverse NPs and their mixtures, while providing novel insights into the multiscale characterization of toxicity mechanisms spanning from molecular interactions to pathway-level information.