Proceedings of the National Academy of Sciences - PNAS, 2017-05, Vol.114 (18), p.E3592-E3601
2017
Details
- Autor(en) / Beteiligte
- Titel
- Effect of cholesterol on the molecular structure and transitions in a clinical-grade lung surfactant extract
- Ist Teil von
- Proceedings of the National Academy of Sciences - PNAS, 2017-05, Vol.114 (18), p.E3592-E3601
- Ort / Verlag
- United States: National Academy of Sciences
- Erscheinungsjahr
- 2017
- Link zum Volltext
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- 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 ¹H–13C 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 |S CH| 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0027-8424eISSN: 1091-6490DOI: 10.1073/pnas.1701239114Titel-ID: cdi_swepub_primary_oai_lup_lub_lu_se_731ab323_3746_4fdb_94ae_2cc4031c9c3f
- Format
- –
- Schlagworte
- Alveoli, Animals, Biological Sciences, Cholesterol, Cholesterol - chemistry, Clinical Medicine, Complex Mixtures - chemistry, Dipolar recoupling, Drugs, Isotopic labeling, Klinisk medicin, Lamellar gels, Lamellar structure, Lipids, Lung - chemistry, Lung surfactant, Lungmedicin och allergi, Lungs, Magnetic spectroscopy, Mass spectrometry, Mass spectroscopy, Medical and Health Sciences, Medicin och hälsovetenskap, Membranes, Molecular structure, NMR, Nuclear magnetic resonance, Order parameter, Order parameters, Phospholipids, Physical Sciences, Physiology, PNAS Plus, Protein Domains, Proteins, Pulmonary Surfactants - chemistry, Respiratory distress syndrome, Respiratory function, Respiratory Medicine and Allergy, Self-assembly, Solid-state nmr, Spectroscopy, Surfactants, Swine, Temperature effects, X-Ray Diffraction, X-ray scattering