Pulmonary surfactant (PS) is a lipid protein mixture found in the alveoli of the lungs. PS reduces the work required to inflate the alveoli by reducing surface tension at the alveolar air-water interface and is actively recycled. Of the four conserved mammalian surfactant proteins, surfactant protein B (SP-B) is the only one capable of facilitating surface tension reduction to near 0 nM/m and consequently is the only one required for survival. It is widely proposed that SP-B, which is highly hydrophobic, allows for minimal surface tension by trafficking specific PS lipids from the alveolar aqueous hypophase to the air-water interface. Inadequate levels of PS and or breakdown of PS are implicated in respiratory distress syndromes (RDS). Current clinical treatments for RDS include intratrachael applications of exogenous PS or synthetic peptides mimicking SP-B, as much of the function of SP-B is preserved by two critical, yet distinctly different, amphiphilic helices at the N- and C-termini. Despite their proven utility in lipid trafficking and improving respiratory function, much remains unknown about the molecular mechanisms underlying PS peptide function. We use ssNMR and EPR techniques to study the interplay between peptide partitioning, lipid dynamics, peptide secondary structure and dynamics, lipid polymorphisms, pH and temperature, providing important insights into lung surfactant function and more generally the enthalpic and entropic contributions underlying amphiphilic peptides interactions with and influence on phospholipid assemblies. NMR and EPR spectroscopy allow us to characterize lipid dynamics, phase behavior, and structure over multiple length- and timescales. Our results highlight lipid- and pH-dependent structural plasticity and unusual amphipathic helical secondary structures which may be important to function. Recent results on developing DNP methodologies to facilitate ssNMR experiments in membrane systems will also be presented.

Peptide-mediated lipid organization, structure, and dynamics in pulmonary surfactant

254th National Meeting (2017)

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