Biophysical Consequences for Exposure of Model Cell Membranes to Perfluoroalkyl Substances

There has been a rising concern about negative impacts of per- and polyfluoroalkyl substances (PFAS) on human and environmental health, given the environmental persistence and bioaccumulation potential of PFAS. In this study, two exemplary PFAS, a long-chain perfluorooctanoic acid (PFOA) and a short-chain alternative perfluorobutanesulfonic acid (PFBS), are investigated to assess their potential to modify bilayers of model membranes formed from 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC). A comprehensive suite of experimental techniques, including water permeability assays, thermal phase behavior analysis (DSC), vibrational spectroscopy (Raman and ATR-FTIR), and evaluations of interfacial properties, reveals concentration-dependent perturbations to DOPC membranes. Water permeability measurements reveal biphasic characteristics in PFAS-membrane interactions, corroborated by phase separation observed via DSC. PFOA and PFBS exhibit distinct impacts on membrane properties, reflecting a sensitivity to PFAS molecular structures. Higher membrane/water partition coefficients for PFOA underscore the role of hydrophobic effect in long- versus short-chain PFAS interactions. PFOA demonstrates a more pronounced effect than PFBS at lower concentrations, but they both exhibit similar impacts on DOPC membranes at higher levels. Notably, PFBS's significant membrane modifications at high concentrations challenge the assumption that shorter-chain PFAS alternatives are inherently safer. These findings highlight the complex nature of PFAS-membrane interactions and emphasize the importance of molecular structure in assessing environmental and health impacts.