Desorption of cholesterol from model membranes by β-cyclodextrins: Characterizing plaque fighting compounds via quartz crystal microgravimetry with dissipation monitoring.

Abstract

Atherosclerosis is induced by low-density lipoprotein cholesterol retention in arterial walls and is identifiable by the presence of atherosclerotic plaques. Supported lipid bilayers (SLBs) are model membrane interfaces that resemble biological cell membranes and can be constructed with various combinations of lipid compositions. Herein, we exploit the solvent-assisted lipid bilayer (SALB) formation method to construct SLB model membranes with varying cholesterol compositions to create a novel lipid-sterol interface atop of biosensors. Cholesterol-laden SLBs are utilized as surfaces where quantitative investigations of various molecules’ cholesterol-fighting competencies can occur. At constant flow, we introduced the cyclodextrins 2-hydroxypropyl-beta-cyclodextrin (HPBCD) and methyl-beta-cyclodextrin (MBCD) atop the membranes of varying cholesterol mol fractions and measured changes in relative areal mass and surface viscosity. Quartz crystal microgravimetry with dissipation monitoring allowed for the collection of these measurements in vitro, overtime. Aggregated experimental desorption data correlates as expected with the relative hydrophobicities and topological polar surface areas of the drug candidates. Data also supports a steady-state kinetic model mechanism for our lipid-cholesterol-drug interface. Overall, our findings demonstrate that MBCD not only removes a distinct quantity of cholesterol greater than that of HPBCD, but MBCD also outperforms the rate constant of cholesterol desorption of HPBCD by a factor of 8.