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Divide & Conquer: surfactant protein SP-C and cholesterol modulate phase segregation in lung surfactant



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Roldán López, Nuria and Pérez Gil, Jesús and Morrow, Michael R. and García Álvarez, Begoña (2017) Divide & Conquer: surfactant protein SP-C and cholesterol modulate phase segregation in lung surfactant. Biophysical Journal, 113 (4). pp. 847-859. ISSN 0006-3495, ESSN: 1542-0086

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Official URL: http://www.cell.com/biophysj/fulltext/S0006-3495(17)30743-9


Lung surfactant (LS) is an essential system supporting the respiratory function. Cholesterol can be deleterious for LS function, a condition that is reversed by the presence of the lipopeptide SP-C. In this work, the structure of LS-mimicking membranes has been analyzed under the combined effect of SP-C and cholesterol by deuterium NMR and phosphorus NMR and by electron spin resonance. Our results show that SP-C induces phase segregation at 37ºC, resulting in an ordered phase with spectral features resembling an interdigitated state enriched in dipalmitoylphosphatidylcholine, a liquid-crystalline bilayer phase, and an extremely mobile phase consistent with small vesicles or micelles. In the presence of cholesterol, POPC and POPG motion seem to be more hindered by SP-C than dipalmitoylphosphatidylcholine. The use of deuterated cholesterol did not show signs of specific interactions that could be attributed to SP-C or to the other hydrophobic surfactant protein SP-B. Palmitoylation of SP-C had an indirect effect on the extent of protein-lipid perturbations by stabilizing SP-C structure, and seemed to be important to maximize differences among the lipids participating in each phase. These results shed some light on how SP-C-induced lipid perturbations can alter membrane structure to sustain LS functionality at the air-liquid interface.

Item Type:Article
Uncontrolled Keywords:Surfactant protein SP-C; Cholesterol; Lung surfactant
Subjects:Medical sciences > Biology > Biochemistry
ID Code:46628
Deposited On:27 Feb 2018 09:07
Last Modified:28 Feb 2018 09:30

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