RT Journal Article T1 Divide & Conquer: surfactant protein SP-C and cholesterol modulate phase segregation in lung surfactant A1 Roldán López, Nuria A1 Pérez-Gil, Jesús A1 Morrow, Michael R. A1 García Álvarez, Begoña AB 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. PB Elsevier SN 0006-3495, ESSN: 1542-0086 YR 2017 FD 2017-08-22 LK https://hdl.handle.net/20.500.14352/18418 UL https://hdl.handle.net/20.500.14352/18418 LA eng NO Ministerio de Economía y Competitividad (MINECO) NO Comunidad de Madrid NO Ministerio de Educación, Cultura y Deporte (MEC) NO Natural Sciences and Engineering Research Council of Canada DS Docta Complutense RD 15 may 2024