Effect of cholesterol on the molecular structure and transitions in a clinical-grade lung surfactant extract [Chemistry]
The lipid–protein film covering the interface of the lung alveolar in mammals is vital for proper lung function and its deficiency
is related to a range of diseases. Here we present a molecular-level characterization of a clinical-grade porcine lung surfactant
extract using a multitechnique approach consisting of
C13 solid-state nuclear magnetic spectroscopy, small- and wide-angle X-ray scattering, and mass spectrometry. The detailed characterization
presented for reconstituted membranes of a lung extract demonstrates that the molecular structure of lung surfactant strongly
depends on the concentration of cholesterol. If cholesterol makes up about 11% of the total dry weight of lung surfactant,
the surfactant extract adopts a single liquid-ordered lamellar phase,
Lα(o), at physiological temperatures. This
Lα(o) phase gradually changes into a liquid-disordered lamellar phase,
Lα(d), when the temperature is increased by a few degrees. In the absence of cholesterol the system segregates into one lamellar
gel phase and one
Lα(d) phase. Remarkably, it was possible to measure a large set of order parameter magnitudes
|SCH| from the liquid-disordered and -ordered lamellar phases and assign them to specific C–H bonds of the phospholipids in the
biological extract with no use of isotopic labeling. These findings with molecular details on lung surfactant mixtures together
with the presented NMR methodology may guide further development of pulmonary surfactant pharmaceuticals that better mimic
the physiological self-assembly compositions for treatment of pathological states such as respiratory distress syndrome.
Publisher URL: http://www.pnas.org/content/114/18/E3592.short
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