Effect of surfactant protein A on the physical properties and surface activity of KL4-surfactant.
SP-A, the major protein component of pulmonary surfactant, is absent in exogenous surfactants currently used in clinical practice. However, it is thought that therapeutic properties of natural surfactants improve after enrichment with SP-A. The objective of this study was to determine SP-A effects on physical properties and surface activity of a new synthetic lung surfactant based on a cationic and hydrophobic 21-residue peptide KLLLLKLLLLKLLLLKLLLLK, KL(4). We have analyzed the interaction of SP-A with liposomes consisting of DPPC/POPG/PA (28:9:5.6, w/w/w) with and without 0.57 mol % KL(4) peptide. We found that SP-A had a concentration-dependent effect on the surface activity of KL(4)-DPPC/POPG/PA membranes but not on that of an animal-derived LES. The surface activity of KL(4)-surfactant significantly improved after enrichment with 2.5-5 wt % SP-A. However, it worsened at SP-A concentrations > or =10 wt %. This was due to the fluidizing effect of supraphysiological SP-A concentrations on KL(4)-DPPC/POPG/PA membranes as determined by fluorescence anisotropy measurements, calorimetric studies, and confocal fluorescence microscopy of GUVs. High SP-A concentrations caused disappearance of the solid/fluid phase coexistence of KL(4)-surfactant, suggesting that phase coexistence might be important for the surface adsorption process.
Sáenz
Alejandra
A
Department of Biochemistry and Molecular Biology I, Complutense University of Madrid, Madrid, Spain.
Cañadas
Olga
O
Bagatolli
Luís A
LA
Sánchez-Barbero
Fernando
F
Johnson
Mark E
ME
Casals
Cristina
C
D000818:Animals; D036341:Intercellular Signaling Peptides and Proteins; D008051:Lipid Bilayers / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry*; D008968:Molecular Conformation; D010455:Peptides / Q000737:chemistry*; D037662:Pulmonary Surfactant-Associated Protein A / Q000737:chemistry*; D013499:Surface Properties; D013552:Swine
D036341:Intercellular Signaling Peptides and Proteins; C097558:KL4 surfactant; D008051:Lipid Bilayers; D008081:Liposomes; D010455:Peptides; D037662:Pulmonary Surfactant-Associated Protein A