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

Area of Science:

• Biochemistry
• Biophysics
• Materials Science

Background:

• Mammalian lung surfactant, a lipid/protein mixture, is vital for reducing alveolar surface tension.
• Surfactant protein SP-B is crucial for surfactant function, but its specific interactions with lipids remain debated.
• Previous studies yielded conflicting results due to varying pH conditions.

Purpose of the Study:

• To investigate the specificity of lipid/SP-B interactions in a model lung surfactant system.
• To determine the influence of pH on the phase behavior of lipids and the distribution of SP-B.
• To elucidate the mechanisms governing SP-B's molecular localization within the lipid mixture.

Main Methods:

• Utilized a model system comprising dipalmitoylphosphatidylcholine (DPPC), dipalmitoylphosphatidylglycerol (DPPG), and SP-B at a 4:1:0.2 mol % ratio.
• Employed fluorescence microscopy to analyze lipid phase behavior.
• Applied laterally resolved time-of-flight secondary ion mass spectrometry (ToF-SIMS) to determine SP-B molecular distribution.

Main Results:

• DPPG formed condensed domains driven by hydrogen bonding, largely excluding SP-B.
• The principle of zone melting (impurity solubility differences between phases) was considered.
• Lipid phase behavior significantly influenced SP-B localization, overriding electrostatic interactions between DPPG and SP-B.
• SP-B colocalization with DPPC was largely passive, driven by lipid phase separation.

Conclusions:

• Lipid phase behavior is the dominant factor in SP-B's molecular distribution within the surfactant model system.
• Electrostatic interactions between DPPG and SP-B play a lesser role compared to lipid phase effects.
• Understanding these interactions is key to comprehending lung surfactant function and potential therapeutic strategies.