Delineation of the dynamic properties of individual lipid species in native and synthetic pulmonary surfactants.
Pulmonary surfactant (PS) is characterized by a highly conserved lipid composition and the formation of unique multilamellar structures within the lung. An unusually high concentration of DPPC is a hallmark of PS and is critical to the formation of a high surface area, stable air/water interface; the unusual lipid polymorphisms observed in PS are dependent on surfactant proteins, particularly lung surfactant protein B (SP-B). The molecular mechanisms of lipid trafficking and assembly in PS remain largely uncharacterized. Using (2)H and (31)P NMR, we characterize the dynamics and polymorphisms of the major lipid species in native PS and synthetic lipid mixtures as a function of SP-B1-25 addition. Our findings point to increased dynamics and a departure from a lamellar behavior for DPPC on addition of the peptide, consistent with our observations of DPPC phase separation in native surfactant. The monounsaturated lipids POPC, POPG and POPE remain in a lamellar phase and are less affected than DPPC by surfactant peptide addition. Additionally, we demonstrate that the properties of a native PS can be successfully mimicked by using a fully synthetic lipid mixture allowing the efficient evaluation of peptidomimetics under development for PS replacement therapies via NMR spectroscopy. The specificity of the dynamic changes in DPPC relative to POPC suggests the importance of tuning partitioning properties in successful peptidomimetic design.
Department of Biochemistry and Molecular Biology, University of Florida, Gainesville, FL 32610, USA.
Suzanne
S
Farver
Department of Chemistry, University of Florida, Gainesville, FL 32611, USA.
Adam N
AN
Smith
Department of Biochemistry and Molecular Biology, University of Florida, Gainesville, FL 32610, USA.
Frank D
FD
Mills
Department of Biochemistry and Molecular Biology, University of Florida, Gainesville, FL 32610, USA.
Adam G
AG
Egri
Department of Biochemistry and Molecular Biology, University of Florida, Gainesville, FL 32610, USA. Electronic address: jrlong@mbi.ufl.edu.
Joanna R
JR
Long
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry; D000595:Amino Acid Sequence; D008055:Lipids / Q000737:chemistry*; D008969:Molecular Sequence Data; D011663:Pulmonary Surfactants / Q000032:analysis*
D008055:Lipids; D011663:Pulmonary Surfactants; D015060:1,2-Dipalmitoylphosphatidylcholine
(2)H NMR; Lipid dynamics; Membrane-active peptide; Pulmonary surfactant; Respiratory distress syndrome; Surfactant protein B