Mechanistic Insights into Bioaccumulation of Perfluoroalkyl Substances (Pfass) Partitioning From Aquatic Environment to Biological Membranes: A Theoretical and Experimental Study

Abstract

Per- and polyfluoroalkyl substances (PFASs) are persistent, bioaccumulative contaminants found in water resources at levels hazardous to human health. However, PFAS bioaccumulation partitioning from aqueous phases to biological membranes remains poorly understood. In this study, we incorporated density functional theory (DFT), molecular dynamics (MD), and experiments to analyze the partitioning pathways and quantify 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 0.835. MD simulations revealed that PFASs spontaneously aggregate into submicelles in aquatic environments, enhancing their bioaccumulation effect. Thermodynamic analysis indicates that PFAS translocation involves spatial flips along the free energy surface: the polar head is initially pulled, then lies flat on the membrane surface, and finally flips and penetrates into the membrane matrix. Consequently, short-chain PFASs exhibit low steric hindrance, contributing to bioaccumulation—a factor previously neglected in research. Furthermore, it was discovered that aggregating PFASs “dissolve” into the lipid membrane matrix, owing significantly to van der Waals interactions rather than electrostatic effects. PFAS bioaccumulation depends on chain length, as further confirmed by intracellular reactive oxygen species formation and live/dead quantification in HepG2 cells.

Keywords: Perfluoroalkyl substance, Bioaccumulation, toxicity, Aggregation, md simulation