Pulmonary Surfactant Protein C Reduces the Size of Liquid Ordered Domains in a Ternary Membrane Model System

Abstract

Surfactant protein C (SP-C) is the smallest pulmonary surfactant protein and is required for the formation and stability of surface-active films at the air-liquid interface in the lung. The protein consists of a hydrophobic transmembrane α-helix and a cationic N-terminal segment, which contains two palmitoylated cysteines. In the present work, we compared the effect of native palmitoylated and recombinant non-palmitoylated versions of full length SP-C on the liquid ordered (lo)/liquid disordered (ld) phase coexistence in a ternary membrane model system consisting of DPPC, DOPC and cholesterol. This model has been previously shown to simulate the phase properties of the lipid components in lung surfactant bilayers and monolayers. Presence of native palmitoylated SP-C reduced the size of lo domains in the DPPC/DOPC/cholesterol membrane model as detected by Forster Resonance Energy Transfer (FRET). Interestingly, very similar effects on the lo/ld equilibrium could be observed in the presence of a recombinant variant of SP-C, in which the two palmitoylcysteines of the native protein had been replaced by phenylalanines. It has been suggested that phenylalanines can act as functional mimics of palmitoylated cysteines in SP-C from some animal species. We therefore propose that the effects of SP-C on domain size could be related to selective interactions of this protein with liquid-ordered membrane regions and that this could be important for SP-C-promoted stabilization of lung surfactant films in vivo.