Hexafluoropropylene oxide trimer acid amplifies cadmium toxicity in Chlorella vulgaris: Insights from interfacial reorganization and multi-omics.

Hexafluoropropylene oxide trimer acid (HFPO-TA), a primary alternative to perfluorooctanoic acid, is increasingly detected in aquatic environments, yet its combined effects with cadmium (Cd2+) remain unclear. Here, we integrated physiological assays, interfacial interactions, and multi-omics analyses to investigate how HFPO-TA modulates Cd2+ toxicity in Chlorella vulgaris. While HFPO-TA alone exhibited negligible toxicity, its presence significantly exacerbated Cd2+-induced growth inhibition, photosynthetic impairment, oxidative stress, and membrane damage. Polysaccharides, proteins, and lipids increased, suggesting a stress-induced shift from growth to energy reserves. HFPO-TA markedly stimulated extracellular polymeric substances secretion and altered algal surface properties (e.g., interfacial binding characteristics and hydrophobicity), promoting Cd adsorption and accumulation. Metabolomics revealed that HFPO-TA amplified Cd2+-induced disturbances in carbohydrate, glutathione-related amino acid, and fatty acid metabolism pathways. Transcriptomic analysis showed that HFPO-TA disrupted photosynthetic compensation under single Cd2+ exposure and enhanced Cd accumulation. Integrated multi-omics further uncovered a molecular mechanism underlying these combined toxic effects. Our findings demonstrate that HFPO-TA, under elevated contaminant exposure conditions, can serve as a toxicity amplifier for Cd2+ in freshwater algae. This combined effect underscores the need to incorporate per- and polyfluoroalkyl substances alternatives and their interactive effects into routine aquatic risk assessment.