Bioaccumulation mechanisms of perfluoroalkyl substances (PFASs) in aquatic environments: Theoretical and experimental insights

Per- and polyfluoroalkyl substances (PFASs) are persistent, bioaccumulative contaminants found in water resources at levels hazardous to human health. However, the PFAS bioaccumulation mechanism remains poorly understood. In this study, we incorporated density functional theory (DFT), molecular dynamics (MD), and experiments to analyze the partitioning pathways and to establish the structure-bioaccumulation relationship. DFT- and MD-calculated environmental fate parameters, comprising LogPO,W, LogPA,W, and diffusion coefficients, coincide with experiments at various ranges of PFAS molecules, with a correction coefficient (R²) of 0.783. MD simulations revealed that medium or long-chain-length PFASs spontaneously aggregate into submicelles in aquatic environments, enhancing their bioaccumulation effect. The short-chain PFASs show weak aggregation, but they also permeate into biological membranes. Particularly, it was discovered that aggregating PFASs “dissolve” into the lipid membrane matrix, owing significantly to van der Waals interactions rather than electrostatic effects. Thermodynamic analysis suggests that PFAS translocation involves spatial flips along the free energy surface. Short-chain PFASs exhibit low steric hindrance, contributing to bioaccumulation—a factor previously neglected in research. PFAS bioaccumulation depends on chain length, as further confirmed by intracellular reactive oxygen species formation and live/dead quantification in HepG2 cells. These insights advance our understanding of PFAS bioaccumulation mechanisms and highlight critical factors influencing their environmental and biological behavior. [Display omitted] •Combined DFT, MD simulations, and experiments to study PFAS bioaccumulation.•PFAS aggregation into submicelles enhances bioaccumulation and toxicity.•PFAS translocation involves spatial flips, aiding bioaccumulation.•Short-chain PFASs show rapid membrane penetration despite low lipid affinity.