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    Structural modifications of lipid membranes exposed to statins - Langmuir monolayer and PM-IRRAS study

    Year: 2020

    Journal: J. Mol. Liq., Volume 313, SEP 1

    Authors: Zaborowska, Michalina; Broniatowski, Marcin; Wydro, Pawel; Matyszewska, Dorota; Bilewicz, Renata

    Organizations: Polish National Science Centre [2018/31/B/ST4/00406]; European Union from the European Regional Development Fund under the Operational Program Innovative Economy, 2007-2013

    Keywords: Statins; Model lipid membrane; Intestinal cell membranes; Langmuir monolayer; Brewster angle microscopy (BAM); Polarization modulation infrared reflection absorption spectroscopy (PM-IRRAS)

    The effects of selected statins on the structure and properties of lipid membranes composed of zwitterionic (1,2-dimyristoyl-sn-glycero-3-phosphocholine, DMPC, 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine, DMPE) or anionic (1,2-dimyristoyl-sn-glycero-3-phospho-l-serine, DMPS) lipids were studied for the first time by Langmuir technique combined with polarization modulation infrared reflection absorption spectroscopy (PM-IRRAS) and Brewster angle microscopy (BAM). The interactions of statins of different hydrophobicity: pravastatin, fluvastatin, and cerivastatin with the polar region of the lipids forming the membrane were monitored by PM-IRRAS and the changes of the overall monolayer structure and organization were described on the basis of surface pressure vs. area per molecule measurements and Brewster angle microscopy. Large differences in the action of each of the statins on the lipid monolayers were observed and explained by their different hydrophobicity combined with the different degree of hydration of the lipid polar headgroups in the monolayer. Monolayer fluidizing effect was connected with the interaction of statins in the headgroup region of the membrane affecting the original hydrogen bonding in the lipid layers. The most hydrophilic pravastatin interacted only with the polar head groups of the monolayer and affected the organization of the polar part of the lipid membrane by increasing the headgroups hydration. In the case of DMPS, the contribution of electrostatic interactions between the negatively charged headgroups and the drug was observed, and for this lipid especially strong dehydration effect of cerivastatin was revealed. It facilitated the incorporation of the hydrophobic part of the drug into the nonpolar region of the DMPS layer and in this case there was almost no fluidization of the layer. Strong dehydration effects may be dangerous for the lipid membranes and may also be one of the reasons to avoid cerivastatin in the therapies, despite its known efficacy especially in view of the large doses and prolonged application that are usually needed. (C) 2020 The Authors. Published by Elsevier B.V.
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