Compatible solutes: ectoine and hydroxyectoine improve functional nanostructures in artificial lung surfactants

Ectoine and hydroxyectoine belong to the family of compatible solutes and are among the most abundant osmolytes in nature. These compatible solutes protect biomolecules from extreme conditions and maintain their native function. In the present study, we have investigated the effect of ectoine and hydroxyectoine on the domain structures of artificial lung surfactant films consisting of dipalmitoylphosphatidylcholine (DPPC), dipalmitoylphosphatidylglycerol (DPPG) and the lung surfactant specific surfactant protein C (SP-C) in a molar ratio of 80:20:0.4. The pressure-area isotherms are found to be almost unchanged by both compatible solutes. The topology of the fluid domains shown by scanning force microscopy, which is thought to be responsible for the biophysical behavior under compression, however, is modified giving rise to the assumption that ectoine and hydroxyectoine are favorable for a proper lung surfactant function. This is further evidenced by the analysis of the insertion kinetics of lipid vesicles into the lipid-peptide monolayer, which is clearly enhanced in the presence of both compatible solutes. Thus, we could show that ectoine and hydroxyectoine enhance the function of lung surfactant in a simple model system, which might provide an additional rationale to inhalative therapy.