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Effect of cholesterol on the molecular structure and transitions in a clinical-grade lung surfactant extract

Andersson, Jenny Marie LU ; Grey, Carl LU ; Larsson, Marcus LU ; Ferreira, Tiago Mendes LU and Sparr, Emma LU (2017) In Proceedings of the National Academy of Sciences of the United States of America 114(18). p.3592-3601
Abstract

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... (More)

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 /SCH/ from the liquiddisordered 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 selfassembly compositions for treatment of pathological states such as respiratory distress syndrome.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Cholesterol, Dipolar recoupling, Lung surfactant, Order parameter, Solid-state nmr
in
Proceedings of the National Academy of Sciences of the United States of America
volume
114
issue
18
pages
3592 - 3601
publisher
National Acad Sciences
external identifiers
  • scopus:85018765483
  • wos:000400358000004
ISSN
0027-8424
DOI
10.1073/pnas.1701239114
language
English
LU publication?
yes
id
731ab323-3746-4fdb-94ae-2cc4031c9c3f
date added to LUP
2017-05-24 08:30:31
date last changed
2017-09-18 11:37:07
@article{731ab323-3746-4fdb-94ae-2cc4031c9c3f,
  abstract     = {<p>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, L<sub>α(o)</sub>, at physiological temperatures. This L<sub>α(o)</sub> 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 L<sub>α(d)</sub> phase. Remarkably, it was possible to measure a large set of order parameter magnitudes /S<sub>CH</sub>/ from the liquiddisordered 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 selfassembly compositions for treatment of pathological states such as respiratory distress syndrome.</p>},
  author       = {Andersson, Jenny Marie and Grey, Carl and Larsson, Marcus and Ferreira, Tiago Mendes and Sparr, Emma},
  issn         = {0027-8424},
  keyword      = {Cholesterol,Dipolar recoupling,Lung surfactant,Order parameter,Solid-state nmr},
  language     = {eng},
  month        = {05},
  number       = {18},
  pages        = {3592--3601},
  publisher    = {National Acad Sciences},
  series       = {Proceedings of the National Academy of Sciences of the United States of America},
  title        = {Effect of cholesterol on the molecular structure and transitions in a clinical-grade lung surfactant extract},
  url          = {http://dx.doi.org/10.1073/pnas.1701239114},
  volume       = {114},
  year         = {2017},
}