title: Hydrophobic surfactant proteins strongly induce negative curvature.
abstract: The hydrophobic surfactant proteins SP-B and SP-C greatly accelerate the adsorption of vesicles containing the surfactant lipids to form a film that lowers the surface tension of the air/water interface in the lungs. Pulmonary surfactant enters the interface by a process analogous to the fusion of two vesicles. As with fusion, several factors affect adsorption according to how they alter the curvature of lipid leaflets, suggesting that adsorption proceeds via a rate-limiting structure with negative curvature, in which the hydrophilic face of the phospholipid leaflets is concave. In the studies reported here, we tested whether the surfactant proteins might promote adsorption by inducing lipids to adopt a more negative curvature, closer to the configuration of the hypothetical intermediate. Our experiments used x-ray diffraction to determine how the proteins in their physiological ratio affect the radius of cylindrical monolayers in the negatively curved, inverse hexagonal phase. With binary mixtures of dioleoylphosphatidylethanolamine (DOPE) and dioleoylphosphatidylcholine (DOPC), the proteins produced a dose-related effect on curvature that depended on the phospholipid composition. With DOPE alone, the proteins produced no change. With an increasing mol fraction of DOPC, the response to the proteins increased, reaching a maximum 50% reduction in cylindrical radius at 5% (w/w) protein. This change represented a doubling of curvature at the outer cylindrical surface. The change in spontaneous curvature, defined at approximately the level of the glycerol group, would be greater. Analysis of the results in terms of a Langmuir model for binding to a surface suggests that the effect of the lipids is consistent with a change in the maximum binding capacity. Our findings show that surfactant proteins can promote negative curvature, and support the possibility that they facilitate adsorption by that mechanism.
authors.affiliation: Department of Biochemistry & Molecular Biology, Oregon Health & Science University, Portland, Oregon; Department of Medicine, Oregon Health & Science University, Portland, Oregon; Department of Physiology & Pharmacology, Oregon Health & Science University, Portland, Oregon.
authors.forename: Mariya
authors.initials: M
authors.lastname: Chavarha
authors.affiliation: Department of Biochemistry & Molecular Biology, Oregon Health & Science University, Portland, Oregon; Department of Medicine, Oregon Health & Science University, Portland, Oregon; Department of Physiology & Pharmacology, Oregon Health & Science University, Portland, Oregon.
authors.forename: Ryan W
authors.initials: RW
authors.lastname: Loney
authors.affiliation: Department of Chemistry, Portland State University, Portland, Oregon.
authors.forename: Shankar B
authors.initials: SB
authors.lastname: Rananavare
authors.affiliation: Department of Biochemistry & Molecular Biology, Oregon Health & Science University, Portland, Oregon; Department of Medicine, Oregon Health & Science University, Portland, Oregon; Department of Physiology & Pharmacology, Oregon Health & Science University, Portland, Oregon. Electronic address: sbh@ohsu.edu.
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Hall
mesh_terms: D008567:Membranes, Artificial; D008956:Models, Chemical; D010713:Phosphatidylcholines / Q000737:chemistry*; D010714:Phosphatidylethanolamines / Q000737:chemistry*; D037701:Pulmonary Surfactant-Associated Protein B / Q000737:chemistry*; D037721:Pulmonary Surfactant-Associated Protein C / Q000737:chemistry*; D013499:Surface Properties; D013696:Temperature
chemical_list: D008567:Membranes, Artificial; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D037701:Pulmonary Surfactant-Associated Protein B; D037721:Pulmonary Surfactant-Associated Protein C; C094877:dioleoyl phosphatidylethanolamine; C017251:1,2-oleoylphosphatidylcholine