Solid-state NMR studies of lung surfactant protein-B fragments in model and natural lung surfactant lipid bilayers

Palleboina, Dharamaraju (2012) Solid-state NMR studies of lung surfactant protein-B fragments in model and natural lung surfactant lipid bilayers. Masters thesis, Memorial University of Newfoundland.

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Abstract

Lung surfactant, a membranous lipid-protein complex, prevents lung collapse by lowering the surface tension at the alveolar air-water interface. Surfactant protein B (SP-B) is an essential component of lung surfactant and is indispensable for life. Mini-B is a two-helix fragment of SP-B that retains significant biological activity compared to the full-length SP-B Solid-state ²H-NMR and ³¹P-NMR were used to characterize the lipid interactions of Mini-B or the combination of the SP-B C-terminal and N-terminal fragments (SP-BCTERM + SP-BNTERM) in mechanically oriented and multilamellar vesicle (MLV) lipid bilayers. These were composed of a model surfactant system, POPC-d₃₁/POPG (7:3) or a natural surfactant system, DPPC-d₆₂-doped Bovine Lipid Extract Surfactant (BLES). Our results show that Mini-B or SP-BCTERM + SP-BNTERM tends to disrupt the bilayer structure and induce the formation of a non-oriented fraction in oriented lipid bilayers on large-scales. Mini-B had a greater effect on oriented bilayers of POPC-d₃₁/POPG than did SP-BCTERM + SP-BNTERM. On the other hand, SP-BCTERM + SP-BNTERM showed more effect on oriented bilayers of BLES than did Mini-B. Neither peptide system significantly changed lipid orientational order in POPC-d₃₁/POPG, whereas the combination of SP-BCTERM + SP-BNTERM did induce some ordering in the oriented fraction of BLES. The interactions of these peptide systems with MLVs were studied in order to separate effects on chain order from large length scale perturbations of bilayer orientation. Neither peptide system induced formation of rapidly tumbling structures in POPC-d₃₁/POPG vesicles whereas both did, to a small extent, in BLES vesicles. Modification of bilayer orientation in oriented lipid bilayers in presence of peptide may be relevant to the transfer of material from bilayer reservoirs to a flat surface active layer, a process that likely requires contact facilitated by the formation of highly curved protrusions. Despite its significant biophysical activity compared to full-length SP-B, Mini-B was not found to enable the formation of tubular myelin, a structure thought to be a precursor to the surface-active layer at the air-water interface.

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