title: Effect of Lung Surfactant Protein SP-C and SP-C-Promoted Membrane Fragmentation on Cholesterol Dynamics.
abstract: To allow breathing and prevent alveolar collapse, lung surfactant (LS) develops a complex membranous system at the respiratory surface. LS is defined by a specific protein and lipid composition, including saturated and unsaturated phospholipid species and cholesterol. Surfactant protein C (SP-C) has been suggested to be an essential element for sustaining the presence of cholesterol in surfactant without functional impairment. In this work, we used a fluorescent sterol-partitioning assay to assess the effect of the surfactant proteins SP-B and SP-C on cholesterol distribution in membranes. Our results suggest that in the LS context, the combined action of SP-B and SP-C appears to facilitate cholesterol dynamics, whereas SP-C does not seem to establish a direct interaction with cholesterol that could increase the partition of free cholesterol into membranes. Interestingly, SP-C exhibits a membrane-fragmentation behavior, leading to the conversion of large unilamellar vesicles into highly curved vesicles ∼25 nm in diameter. Sterol partition was observed to be sensitive to the bending of bilayers, indicating that the effect of SP-C to mobilize cholesterol could be indirectly associated with SP-C-mediated membrane remodeling. Our results suggest a potential role for SP-C in generating small surfactant structures that may participate in cholesterol mobilization and pulmonary surfactant homeostasis at the alveolar interfaces.
authors.affiliation: Department of Biochemistry and Molecular Biology I, Complutense University, Madrid, Spain.
authors.forename: Nuria
authors.initials: N
authors.lastname: Roldan
authors.affiliation: Biochemistry, Faculty of Science and Engineering, Åbo Akademi University, Turku, Finland.
authors.forename: Thomas K M
authors.initials: TKM
authors.lastname: Nyholm
authors.affiliation: Biochemistry, Faculty of Science and Engineering, Åbo Akademi University, Turku, Finland.
authors.forename: J Peter
authors.initials: JP
authors.lastname: Slotte
authors.affiliation: Department of Biochemistry and Molecular Biology I, Complutense University, Madrid, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Pérez-Gil
authors.affiliation: Department of Biochemistry and Molecular Biology I, Complutense University, Madrid, Spain. Electronic address: begoga01@ucm.es.
authors.forename: Begoña
authors.initials: B
authors.lastname: García-Álvarez
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002462:Cell Membrane / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism*; D002784:Cholesterol / Q000737:chemistry / Q000378:metabolism*; D037701:Pulmonary Surfactant-Associated Protein B / Q000494:pharmacology; D037721:Pulmonary Surfactant-Associated Protein C / Q000737:chemistry / Q000494:pharmacology*; D013499:Surface Properties; D013552:Swine
chemical_list: D037701:Pulmonary Surfactant-Associated Protein B; D037721:Pulmonary Surfactant-Associated Protein C; D002784:Cholesterol