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Statin Action Targets Lipid Rafts of Cell Membranes: GIXD/PM-IRRAS Investigation of Langmuir Monolayers

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cris.lastimport.scopus2024-02-12T19:56:04Z
dc.abstract.enLipid rafts are condensed regions of cell membranes rich in cholesterol and sphingomyelin, which constitute the target for anticholesterolemic drugs - statins. In this work, we use for the first time a combined grazing-incidence X-ray diffraction (GIXD)/polarization modulation infrared reflection absorption spectroscopy (PM-IRRAS)/Brewster angle microscopy (BAM) approach to show the statin effect on model lipid rafts and its components assembled in Langmuir monolayers at the air–water interface. Two representatives of these drugs, fluvastatin (FLU) and cerivastatin (CER), of different hydrophobicity were chosen, while cholesterol (Chol) and sphingomyelin (SM), and their 1:1 mixture were selected to form condensed monolayers of lipid rafts. The effect of statins on the single components of lipid rafts indicated that both the hydrophobicity of the drugs and the organization of the layer determined the drug–lipid interaction. For cholesterol monolayers, only the most hydrophobic CER was effectively changing the film structure, while for the less organized sphingomyelin, the biggest effect was observed for FLU. This drug affected both the polar headgroup region as shown by PM-IRRAS results and the 2D crystalline structure of the SM monolayer as evidenced by GIXD. Measurements performed for Chol/SM 1:1 models proved also that the statin effect depends on the presence of Chol–SM complexes. In this case, the less hydrophobic FLU was not able to penetrate the binary layer at all, while exposure to the hydrophobic CER resulted in the phase separation and formation of ordered assemblies. The changes in the membrane properties were visualized by BAM images and GIXD patterns and confirmed by thermodynamic parameters of hysteresis in the Langmuir monolayer compression–decompression experiments.
dc.affiliationUniwersytet Warszawski
dc.contributor.authorMatyszewska, Dorota
dc.contributor.authorBilewicz, Renata
dc.contributor.authorFontaine, Philippe
dc.contributor.authorBroniatowski, Marcin
dc.contributor.authorZaborowska, Michalina
dc.date.accessioned2024-01-26T08:08:27Z
dc.date.available2024-01-26T08:08:27Z
dc.date.copyright2023-08-08
dc.date.issued2023
dc.description.accesstimeAT_PUBLICATION
dc.description.financeNie dotyczy
dc.description.number32
dc.description.versionFINAL_PUBLISHED
dc.description.volume127
dc.identifier.doi10.1021/ACS.JPCB.3C02574
dc.identifier.issn1520-6106
dc.identifier.urihttps://repozytorium.uw.edu.pl//handle/item/120653
dc.identifier.weblinkhttps://pubs.acs.org/doi/pdf/10.1021/acs.jpcb.3c02574
dc.languageeng
dc.pbn.affiliationchemical sciences
dc.relation.ispartofJournal of Physical Chemistry B
dc.relation.pages7135-7147
dc.rightsCC-BY
dc.sciencecloudnosend
dc.titleStatin Action Targets Lipid Rafts of Cell Membranes: GIXD/PM-IRRAS Investigation of Langmuir Monolayers
dc.typeJournalArticle
dspace.entity.typePublication