Inhomogenitäten und Phasenseparation in Lipid-Extrakten der Lunge
Zusammenfassung der Projektergebnisse
The initial aim and goals of the project were partially accomplished. The proposed goal was to study the phase behavior in a lung surfactant extract and in the related model system ternary mixture DPPC/DOPC/ cholesterol. Two main findings were achieved: • One main finding was that the presence of cholesterol significantly alters the properties of a lung surfactant extract. Currently, the lung surfactant extracts used in clinics are most often depleted of cholesterol. It is known however that there is a significant amount of cholesterol in the native lung surfactant. We have demostrated by means of a combination of solidstate NMR, X-ray scattering and mass spectrometry methods that the absence of cholesterol in a lung surfactant extract induces the appearance of a gel-phase coexisting with a liquid disordered lamellar phase and that the addition of cholesterol (similarly as in a DPPC/DOPC/cholesterol mixture) leads to the disruption of the gel-phase in favor of a fully liquid membrane system with acyl chain ordering. • The second main finding was to demonstrate that it is possible to use dipolar recoupling NMR to detect liquid-liquid phase coexistence in a DPPC/DOPC/cholesterol ternary lipid system. This was the first time that an NMR method which does not require adding any isotopic labeling was used to detect liquid-liquid phase coexistence in a membrane system. This motivates the use of this methodology on biological samples for which liquid-liquid phase coexistence may be expected and for which the presently used methods are not applicable without manipulating the system for including molecular probes which may alter (locally or even on the µm scale) the lipid phase behavior. In the future we want to continue to optimize the presently used NMR experiments and also test new methodology on both simple binary/ternary systems to use these methods on lipid-based biological matter such as native lung surfactant and myelin.
Projektbezogene Publikationen (Auswahl)
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Effect of cholesterol on the molecular structure and transitions in a clinicalgrade lung surfactant extract. Proc. Natl. Acad. Sci. USA 114, E3592 (2017)
J. M. Andersson, C. Grey, M. Larsson, T. M. Ferreira and E. Sparr
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Cholesterol-like effects of a fluorotelomer alcohol incorporated in phospholipid membranes. Scientific Reports 8, 2154 (2018)
M. Jbeily, R. Bärenwald, J. Kressler, K. Saalwächter and T. M. Ferreira
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Liquid-liquid phase coexistence in lipid membranes observed by natural abundance 1 H–13 C solid-state NMR, Phys. Chem. Chem. Phys. 20, 9751 (2018)
L. Löser, K. Saalwächter and T. M. Ferreira
