The effect of perfluorooctadecanoic acid on a model phosphatidylcholine–peptide pulmonary lung surfactant mixture

Abstract Fluorinated surface active molecules have demonstrated potential for applications in pulmonary surfactant replacement therapy. To characterize molecular-level interactions between constituents in model replacement formulations, the mixing thermodynamics, surfactant recovery and morphology of a mixed surfactant monolayer containing a phospholipid, a perfluorinated fatty acid and a peptide-based mimetic of a pulmonary surfactant protein has been investigated at the air–water interface. The synthetic peptide (amino acid sequence KLLKLLLKLCLKLLKLLL; KLL) was added to mixed films of 1,2-dipalmitoyl- sn -glycero-3-phosphocholine (DPPC) and perfluorooctadecanoic acid (C18F) on a simplified lung fluid mimic subphase (pH 7.4, 150 mM NaCl), and compression isotherms of the films were used to extract excess Gibbs free energies of mixing, along with hysteresis (surfactant recovery) response data. It was observed that, at low peptide content, KLL mixed non-ideally with the other film components, exhibiting negative deviations from ideality. Surfactant recovery upon repeated compression-expansion cycles for ternary films that contained DPPC, C18F and KLL were comparable with mixed DPPC–C18F films, indicating that this performance parameter is only minimally improved by the addition of the peptide. Film morphologies were significantly different for the peptide-containing mixed monolayers in comparison with control samples containing DPPC alone or DPPC–C18F, with films consisting of discrete DPPC-rich domains that tended to fuse as a function of increased film compression. Mixing thermodynamics, film structures and behavior upon compression are discussed in the context of affiliated systems described previously in the literature.