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    Surface and electrochemical properties of lipid raft model membranes and how they are affected by incorporation of statin

    Year: 2021

    Journal: Electrochim. Acta, Volume 386, AUG 1

    Authors: Zaborowska, Michalina; Dziubak, Damian; Matyszewska, Dorota; Bilewicz, Renata

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

    Keywords: Lipid rafts; Langmuir-blodgett monolayer; Electrochemical impedance spectroscopy; Statins

    Cerivastatin belongs to the class of statins, drugs lowering blood cholesterol level by inhibiting the enzyme HMG-CoA reductase. The enzyme is located in the endoplasmic reticulum (ER) membrane, which is enriched in cholesterol and sphingolipids. Therefore, in the present study an equimolar mixture of 1,2-dioleoylo-sn-glycero-3-phosphocholine (DOPC), cholesterol (Chol) and egg sphingomyelin (SM) was used to prepare a simple model of the ER membrane using the Langmuir technique. DOPC:Chol:SM 1:1:1 monolayers were characterized by surface pressure measurements and Brewster angle microscopy (BAM). The lipid raft formation was confirmed by a characteristic kink on the surface pressure - area per molecule (pi-A) isotherm. Exposure of the model membrane to solutions containing cerivastatin led to the fluidization of the membranes, confirmed by the BAM images. The lipid monolayers were next transferred using the combined Langmuir-Blodgett (LB) - Langmuir-Schaefer (LS) approach onto the gold (111) substrates and the resulting supported bilayer was studied using electrochemical impedance spectroscopy (EIS). EIS measurements showed inhomogeneity of the bilayer and the presence of defects occurring on the borders of the raft islands. However, upon exposure to cerivastatin, part of these defects disappeared - they were filled with the statin molecules, which changed the properties of the bilayer. The disappearance of the minimum on the phase angle plot and impedance measurement data confirmed the decrease in the defectiveness of the layer - the resistance of the membrane increased while its capacitance decreased. The hydrophobic drug penetration into the hydrophobic core of the lipid layer led to increased barrier properties of the film despite its increased fluidity. Such serious modification of lipid membranes under influence of cerivastatin is one of the unwanted side effects of this drug and although it effectively decreased cholesterol levels in the body, its withdrawal from the pharmaceutical market had to be considered. (C) 2021 The Author(s). Published by Elsevier Ltd.
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