The Hydrophobic Surfactant Proteins Strongly Induce Lipid Curvature

Abstract

The hydrophobic surfactant proteins, SP‐B and SP‐C, greatly accelerate adsorption by vesicles of the surfactant lipids to form a film that lowers the surface tension in the lungs. Pulmonary surfactant enters the interface by a process analogous to the fusion of two vesicles. Like fusion, several factors affect adsorption according to how they alter the curvature of lipid leaflets, and suggest that adsorption proceeds via a rate‐limiting structure with negative curvature, in which the hydrophilic face of the phospholipid leaflets is concave. The studies reported here tested whether the surfactant proteins might promote adsorption by inducing the lipids to adopt more negative curvature, closer to the configuration of the hypothetical intermediate. We 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 dioleoyl phosphatidylethanolamine (DOPE) and dioleoyl phosphatidylcholine (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 increasing amounts 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. Our findings show that the surfactant proteins can promote negative curvature, and support the possibility that they facilitate adsorption by that mechanism.