Solubility versus electrostatics: What determines lipid/protein interaction in lung surfactant

Mammalian lung surfactant is a complex lipid/ protein mixture covering the alveolar interface and has the crucial function of reducing the surface tension at this boundary to minimal values. Surfactant protein SP- B plays an important role for this purpose and was the focus of many recent studies. However, the specificity of lipid/ SP- B interactions is controversial. Since these investigations were accomplished at varying pH conditions (pH 5.5 and 7.0), we studied the specificity of these interactions in a dipalmitoylphosphatidylcholine (DPPC)/dipalmitoylphosphatidylglycerol (DPPG)/ SP- B ( 4: 1: 0.2 mol %) model system at either pH. Mainly fluorescence microscopy and laterally resolved time-of-flight secondary ion mass spectrometry were used to reveal information about the phase behavior of the lipids and the molecular distribution of SP- B in the lipid mixture. DPPG forms separated condensed domains due to a strong hydrogen- bond network, from which the protein is mainly excluded. Considering the protein as an impurity of the lipid mixture leads to the principle of the zone melting process: an impurity is highly more soluble in a liquid phase than in a solid phase. The phase behavior effect of the lipids mainly outperforms the electrostatic interactions between DPPG and SP-B, leading to a more passively achieved colocalization of DPPC and SP- B.