Membrane-Modifying Effects of Perfluoroalkyl Substances in Model Bacterial Membranes.

Understanding the interactions of per- and polyfluoroalkyl substances (PFAS) with bacterial membranes is essential for evaluating their ecological and health impacts. To mimic the diverse environments found in bacterial membranes, we constructed model membranes as bilayers, liposomes, and supported bilayers using binary lipid mixtures of 1,2-dioleoyl--glycero-3-phosphocholine (DOPC) or 1,2-dioleoyl--glycero-3-phosphoethanolamine (DOPE), with 1,2-dioleoyl--glycero-3-phospho-(1'-rac-glycerol) (sodium salt) (DOPG)all sharing the same acyl chains but differing in headgroup types and charges. Our findings demonstrate that salts of perfluorooctanoic acid (PFOA) and perfluorobutanesulfonic acid (PFBS) induce concentration- and lipid-dependent disordering effect in membranes composed of DOPC/DOPG (3:1 mol ratio) and DOPE/DOPG (3:1 mol ratio). Water permeability measurements reveal that membranes with greater hydrogen bonding capacity and curvature stresssuch as those containing DOPEexhibit more pronounced increases in permeability upon PFAS exposure, indicating heightened susceptibility to disruption by these contaminants. Differential scanning calorimetry (DSC) shows that DOPE-DOPG mixtures display a more significant decrease in phase transition temperature ( ) and enthalpy compared to DOPC-DOPG membranes. Moreover, Raman and attenuated total reflectance infrared (ATR-IR) spectroscopies reveal a greater increase in lipid acyl chain disorder in DOPE-DOPG mixtures upon PFAS exposure. Collectively, these findings indicate that PFAS salts not only increase membrane permeability but also destabilize lipid packing and phase organization, with the most pronounced disordering effects observed in membranes containing DOPE. Taken together, our results highlight the complex interplay of electrostatic, van der Waals, and hydrogen bonding interactions that govern the effects of PFAS salts on bacterial membrane properties, as revealed by their differential impacts on permeability and lipid organization.