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* Department of Biochemistry and Molecular Biology I, Complutense University of Madrid, Madrid, Spain;
MEMPHYS-Center for Biomembrane Physics, Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark; and
Discovery Laboratories, Mountain View, California
Correspondence: Address reprint requests to Cristina Casals, Dept. of Biochemistry and Molecular Biology I, Faculty of Biology, Complutense University of Madrid, 28040 Madrid, Spain. Tel.: 34-91-3944261; Fax: 34-91-3944672; E-mail: ccasalsc{at}bio.ucm.es.
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, KL4. 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 % KL4 peptide. We found that SP-A had a concentration-dependent effect on the surface activity of KL4-DPPC/POPG/PA membranes but not on that of an animal-derived LES. The surface activity of KL4-surfactant significantly improved after enrichment with 2.55 wt % SP-A. However, it worsened at SP-A concentrations
10 wt %. This was due to the fluidizing effect of supraphysiological SP-A concentrations on KL4-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 KL4-surfactant, suggesting that phase coexistence might be important for the surface adsorption process.
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O. Canadas, I. Garcia-Verdugo, K. M. W. Keough, and C. Casals SP-A Permeabilizes Lipopolysaccharide Membranes by Forming Protein Aggregates that Extract Lipids from the Membrane Biophys. J., October 1, 2008; 95(7): 3287 - 3294. [Abstract] [Full Text] [PDF] |
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