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

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Standard

Effect of cholesterol on the molecular structure and transitions in a clinical-grade lung surfactant extract. / Andersson, Jenny Marie; Grey, Carl; Larsson, Marcus; Ferreira, Tiago Mendes; Sparr, Emma.

I: Proceedings of the National Academy of Sciences of the United States of America, Vol. 114, Nr. 18, 02.05.2017, s. E3592-E3601.

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Harvard

APA

CBE

MLA

Vancouver

Author

RIS

TY - JOUR

T1 - Effect of cholesterol on the molecular structure and transitions in a clinical-grade lung surfactant extract

AU - Andersson, Jenny Marie

AU - Grey, Carl

AU - Larsson, Marcus

AU - Ferreira, Tiago Mendes

AU - Sparr, Emma

PY - 2017/5/2

Y1 - 2017/5/2

N2 - 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.

AB - 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.

KW - Cholesterol

KW - Dipolar recoupling

KW - Lung surfactant

KW - Order parameter

KW - Solid-state nmr

UR - http://www.scopus.com/inward/record.url?scp=85018765483&partnerID=8YFLogxK

U2 - 10.1073/pnas.1701239114

DO - 10.1073/pnas.1701239114

M3 - Article

VL - 114

SP - E3592-E3601

JO - Proceedings of the National Academy of Sciences

T2 - Proceedings of the National Academy of Sciences

JF - Proceedings of the National Academy of Sciences

SN - 1091-6490

IS - 18

ER -