RT Journal Article T1 Physical properties and surface activity of surfactant-like membranes containing the cationic and hydrophobic peptide KL4 A1 Sáenz, Alejandra A1 Cañadas Benito, Olga A1 Bagatolli, Luís A1 Johnson, Mark A1 Casals Carro, María Cristina AB Surfactant-like membranes containing the 21-residue peptide KLLLLKLLLLKLLLLKLLLLK (KL4), have been clinically tested as a therapeutic agent for respiratory distress syndrome in premature infants. The aims of this study were to investigate the interactions between the KL4 peptide and lipid bilayers, and the role of both the lipid composition and KL4 structure on the surface adsorption activity of KL4-containing membranes. We used bilayers of three-component systems [1,2-dipalmitoyl-phosphatidylcholine ⁄ 1-palmitoyl-2-oleoyl-phosphatidylglycerol ⁄ palmitic acid (DPPC⁄POPG⁄ PA) and DPPC⁄ 1-palmitoyl-2-oleoyl-phosphatidylcholine (POPC) ⁄PA] and binary lipid mixtures of DPPC⁄POPG and DPPC⁄PA to examine the specific interaction of KL4 with POPG and PA. We found that, at low peptide concentrations, KL4 adopted a predominantly a-helical secondary structure in POPG- or POPC-containing membranes, and a b-sheet structure in DPPC⁄PA vesicles. As the concentration of the peptide increased, KL4 interconverted to a b-sheet structure in DPPC⁄POPG⁄PA or DPPC⁄POPC⁄PA vesicles. Ca2+ favored a«b interconversion. This conformationalflexibility of KL4 did not influence the surface adsorption activity of KL4-containing vesicles. KL4 showed a concentration-dependent ordering effect on POPG- and POPC-containing membranes, which could be linked to its surface activity. In addition, we found that the physical state of the membrane had a critical role in the surface adsorption process. Our results indicate that the most rapid surface adsorption takes place with vesicles showing well-defined solid ⁄ fluid phase co-existence at temperatures below their gel to fluid phase transition temperature, such as those of DPPC⁄POPG⁄PA and DPPC⁄POPC⁄ PA. In contrast, more fluid (DPPC⁄POPG) or excessively rigid (DPPC⁄ PA) KL4-containing membranes fail in their ability to adsorb rapidly onto and spread at the air–water interface. PB Wiley SN 1742-464X YR 2006 FD 2006 LK https://hdl.handle.net/20.500.14352/93151 UL https://hdl.handle.net/20.500.14352/93151 LA eng NO Sáenz A, Cañadas O, Bagatolli LA, Johnson ME, Casals C. Physical properties and surface activity of surfactant-like membranes containing the cationic and hydrophobic peptide KL4. FEBS J. 2006 Jun; 273: 2515–27 NO Ministerio de Sanidad (España) NO Dr Esteve, S.A. Laboratorios (Barcelona) NO Independent Research Fund (Denmark) NO Danish National Research Foundation DS Docta Complutense RD 17 abr 2025