Perfluoroalkyl acids (PFA) are amphiphilic surfactants widely used in industry with several commercial applications. An important feature of these compounds is their non-biodegradability and their tendency to bio-accumulate in the environment, which has led to these compounds being considered among the most persistent pollutants worldwide. Many studies have provided evidence of their toxic effect on humans and wildlife. For this reason, more and more efforts have been made to better understand the effect of these compounds on living organisms. The aim of the present study is to understand how the electrostatic interactions and film compactness of biological membrane models modulate their interaction with PFA, more specifically with perfluorodecanoic acid (PFD). Langmuir isotherms and Brewster angle microscopy (BAM) are used to evaluate the effect of PFD on lipid membrane models (air/water monolayers and vesicles), analyzing the behavior of PFD : lipid mixtures. The lipids used in this study are distearoyl phosphatidic acid (DSPA), dilauroyl phosphatidic acid (DLPA) and distearoyl phosphatidylethanolamine (DSPE). PFD induces an increase in the mean molecular area per lipid in monolayers, mainly at lower surface pressures. BAM images demonstrate that PFD mixes with DLPA, inducing a decrease in gray level, while it forms a non-miscible mixture with DSPA, segregating PFD domains. Insertion studies of PFD within monolayers and dynamic light scattering experiments demonstrate that PFD can penetrate into monolayers and bilayers above 30 mN m-1, which is the lateral pressure value accepted for a cellular bilayer.