Impact of oxidized phospholipids on the structural and dynamic organization of phospholipid membranes: a combined DSC and solid state NMR study
2013 (English)In: Faraday discussions (Online), ISSN 1359-6640, E-ISSN 1364-5498, Vol. 161, 499-513 p.Article in journal (Refereed) Published
Membranes undergo severe changes under oxidative stress conditions due to the creation of oxidized phospholipid (OxPls) species which possess molecular properties quite different from their parental lipid components. These OxPls play crucial roles in various pathological disorders and their occurrence is involved in the onset of intrinsic apoptosis, a fundamental pathway in programmed mammalian cell death. However, the molecular mechanisms by which these lipids can exert their apoptotic action via their host membranes (e.g. altering membrane protein function) are poorly understood. Therefore, we studied the impact of OxPls on the organization and biophysical properties of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) based lipid membranes by differential scanning calorimetry (DSC) and solid state nuclear magnetic resonance (NMR) spectroscopy. Incorporation of defined OxPls with either a carboxyl group (1-Palmitoyl-2-azelaoyl-sn-glycero-3-phosphocholine (PazePC)) or aldehyde (1-Palmitoyl-(9´oxononanoyl)-sn-glycero-3-phosphocholine (PoxnoPC)) at their truncated sn-2-chain ends enabled us to reveal OxPls species dependent differences. The calorimetric studies revealed significant effects of OxPls on the thermotropic phase behavior of DMPC bilayers, especially at elevated levels where PazePC induced more pronounced effects than PoxnoPC. Temperature dependent changes in the solid state 31P NMR spectra which provided information of the of lipid headgroup region in these mixed membrane system, reflected this complex phase behavior. In the temperature region between 293 K (onset of L-phase) and 298 K two overlapping NMR spectra were visible which reflect the co-existence of two liquid-crystalline lamellar phases with presumably one reflecting OxPls-poor domains and the other OxPls-rich domains. Deconvolution of the DSC profiles also revealed these two partially overlapping thermal events. In addition, also a third thermal, non NMR-visible, event occurred at low temperatures, which mostly likely can be associated with a solid-phase mixing/demixing process of the OxPl-containing membranes. The observed phase transitions were moved to higher temperatures in the presence of heavy water due its condensing effect, where additional wideline 2H NMR studies revealed a complex hydration pattern in the presence of OxPls.
Place, publisher, year, edition, pages
RSC Publishing, 2013. Vol. 161, 499-513 p.
IdentifiersURN: urn:nbn:se:umu:diva-58036DOI: 10.1039/C2FD20089AOAI: oai:DiVA.org:umu-58036DiVA: diva2:546626
First published online 27 Jun 20122012-08-242012-08-242015-10-28Bibliographically approved