The surfactant peptide KL4 in lipid monolayers: phase behavior, topography, and chemical distribution.
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. KL4 ([lysine-(leucine)4]4-lysine) is a synthetic peptide based on SP-B structure and is the major constituent of Surfaxin, a potential therapeutic agent for respiratory distress syndrome in premature infants. There is, however, no clear understanding about the possible lipid-KL4 interactions behind its function, which is an inevitable knowledge to design improved therapeutic agents. To examine the phase behavior, topography, and lipid specificity of KL4/lipid systems, we aimed to study different surfactant model systems containing KL4, neutral dipalmitoylphosphatidylcholine (DPPC) and/or negatively charged dipalmitoylphosphatidylglycerol (DPPG) in the presence of Ca2+ ions. Surface pressure-area isotherms, fluorescence microscopic images, scanning force microscopy as well as time-of-flight secondary ion mass spectrometry suggest (i) that KL4 is not miscible with DPPC and therefore forms peptide aggregates in DPPC/KL4 mixtures; (ii) that KL4 specifically interacts with DPPG via electrostatic interactions and induces percolation of DPPG-rich phases; (iii) that existing DPPG-Ca2+ interactions are too strong to be overcome by KL4, 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.
Saleem
Mohammed
M
Institute of Biochemistry, University of Muenster, Muenster 48149, Germany and Tascon GmbH, Muenster 48149, Germany.
Meyer
Michaela C
MC
Breitenstein
Daniel
D
Galla
Hans-Joachim
HJ
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry*; D000818:Animals; D002118:Calcium / Q000737:chemistry; D036341:Intercellular Signaling Peptides and Proteins; D008567:Membranes, Artificial; D010455:Peptides / Q000737:chemistry*; D010715:Phosphatidylglycerols / Q000737:chemistry*; D037701:Pulmonary Surfactant-Associated Protein B / Q000737:chemistry; D013329:Structure-Activity Relationship
D036341:Intercellular Signaling Peptides and Proteins; C097558:KL4 surfactant; D008567:Membranes, Artificial; D010455:Peptides; D010715:Phosphatidylglycerols; D037701:Pulmonary Surfactant-Associated Protein B; D015060:1,2-Dipalmitoylphosphatidylcholine; D002118:Calcium; C030345:1,2-dipalmitoylphosphatidylglycerol