PFOA Induces Fission of Phase-Separated Phospholipid Vesicles

Per- and polyfluoroalkyl substances (PFAS) are known for their strong surface activity and non-decaying characteristics. The amphiphilicity of these molecules makes them easy to penetrate and disrupt cellular membranes, leading to bioaccumulation in organisms. Here, we investigate the interaction between phospholipid vesicles and perfluorooctanoic acid (PFOA), one of the most widespread PFAS species in the environment. In particular, we examine how the introduction of PFOA perturbs phase-separated ternary (DOPC/DPPC/Chol) vesicles, as a model system for cellular membranes. We show experimentally that PFOA induces a rapid fission of the vesicle along the phase boundary. This results in the formation of two distinct vesicles; one in liquid-disordered (LD ) phase and the other in liquid-ordered (LO) phase. All-atom molecular dynamics simulations and free energy analysis suggest that the mechanism behind the fission process is attributed to the drastic change in the spontaneous curvature of LD phase (DOPC/Chol) of the vesicle upon interacting with PFOA. Our findings reveal the significance of PFAS on the dynamics of phase-separated vesicles, implying a potential disruptive impact of PFAS exposure on cellular membranes.