Effect of PFAS Molecules on Model Membrane Physical Properties via Atomistic Simulation

Per- and polyfluoroalkyl substances (PFAS) are emerging contaminants whose strong surface activity suggests a capacity to perturb cell membranes, yet their effects on bilayer mechanics remain understudied. We investigate how PFAS chemistry affects the interaction with various phospholipid bilayers and modulates their physical properties using all-atom molecular dynamics. Two representative PFAS molecules are considered: legacy anionic perfluorooctanoic acid (PFOA) and zwitterionic 5:3 fluorotelomer betaine (FTB). The effects of PFOA protonation states and salt concentration on the free energy of membrane interaction are first studied for model bilayers consisting of mixtures of DOPC/Cholesterol and DPPC/Cholesterol. Simulations consider multiple PFAS insertions into a single-component POPC bilayer at varying concentrations to characterize the membrane response. Our analysis includes PFAS distributions in lipid bilayer, membrane structural properties (area per lipid, thickness, acyl-chain order parameters), and mechanical properties (area-compressibility modulus and rupture strength under biaxial expansion). This molecular-level analysis provides insight into how environmentally relevant PFAS alter lipid bilayer organization and mechanics.