An Impedance-Based Approach for Sensing Cyclodextrin-Mediated Modulation of Membrane Cholesterol

Cyclodextrin molecules are increasingly being used inbiologicalresearch and as therapeutic agents to alter membrane cholesterol content,yet there is much to learn about their interactions with cell membranes.We present a biomembrane-based organic electronic platform capableof detecting interactions of cell membrane constituents with methyl-& beta;-cyclodextrin(M & beta;CD). This approach enables label-free sensing and quantificationof changes in membrane integrity resulting from such interactions.In this work, we employ cholesterol-containing supported lipid bilayers(SLBs) formed on conducting polymer-coated electrodes to investigatehow M & beta;CD impacts membrane resistance. By examining the outcomesof M & beta;CD interactions with SLBs of varying cholesterol content,we demonstrate that changes in membrane permeability or resistancecan be used as a functional measure for predicting cyclodextrin-mediatedcholesterol extraction from cellular membranes. Furthermore, we usethe SLB platforms to electronically monitor cholesterol delivery tomembranes following exposure to M & beta;CD pre-loaded with cholesterol,observing that cholesterol enrichment is commensurate with an increasein resistance. This biomembrane-based bioelectronic sensing systemoffers a tool to quantify the modulation of membrane cholesterol contentusing membrane resistance and provides information regarding M & beta;CD-mediatedchanges in membrane integrity. Given the importance of membrane integrityfor barrier function in cells, such knowledge is essential for ourfundamental understanding of M & beta;CD as a membrane cholesterolmodulator and therapeutic delivery vehicle.