The Surfactant Peptide KL sub(4) in Lipid Monolayers: PHASE BEHAVIOR, TOPOGRAPHY, AND CHEMICAL DISTRIBUTION

• Published in: The Journal of biological chemistry Vol. 283; no. 8; pp. 5195 - 5207
• Main Authors: Saleem, Mohammed, Meyer, Michaela C, Breitenstein, Daniel, Galla, Hans-Joachim
• Format: Journal Article
• Language: English
• Published: 01-02-2008
• ISSN: 0021-9258; 1083-351X

Studies of different fragments and mutants of SP-B suggest that the function related structural and compositional characteristics in SP-B are its positive charges with intermittent hydrophobic domains. KL sub(4) ([lysine-(leucine) sub(4)] sub(4)-lysine) is a synthetic peptide based on SP-B structure and is the major constituent of Surfaxin registered , a potential therapeutic agent for respiratory distress syndrome in premature infants. There is, however, no clear understanding about the possible lipid-KL sub(4) interactions behind its function, which is an inevitable knowledge to design improved therapeutic agents. To examine the phase behavior, topography, and lipid specificity of KL sub(4)/lipid systems, we aimed to study different surfactant model systems containing KL sub(4), neutral dipalmitoylphosphatidylcholine (DPPC) and/or negatively charged dipalmitoylphosphatidylglycerol (DPPG) in the presence of Ca super(2+) ions. Surface pressure-area isotherms, fluorescence microscopic images, scanning force microscopy as well as time-of-flight secondary ion mass spectrometry suggest (i) that KL sub(4) is not miscible with DPPC and therefore forms peptide aggregates in DPPC/KL sub(4) mixtures; (ii) that KL sub(4) specifically interacts with DPPG via electrostatic interactions and induces percolation of DPPG-rich phases; (iii) that existing DPPG-Ca super(2+) interactions are too strong to be overcome by KL sub(4), the reason why the peptide remains excluded from condensed DPPG domains and passively colocalizes with DPPC in a demixed fluid phase; and (iv) that the presence of negatively charged lipid is necessary for the formation of bilayer protrusions. These results indicate that the capability of the peptide to induce the formation of a defined surface-confined reservoir depends on the lipid environment, especially on the presence of anionic lipids.