Evaluating the Cell Membrane Penetration Potential of Lipid-Soluble Compounds Using Supported Phospholipid Bilayers

Supported phospholipid bilayers (SPBs) are promising models for studying the passive penetration of lipid-soluble compounds into cells and cell membranes. A widely used tool to characterize molecular SPB interactions is the quartz crystal microbalance with dissipation monitoring (QCM-D). As QCM-D provides access to the mass density of supported membranes, it is well-suited to examine surface adsorption and membrane disruption phenomena. In the present study, we report on a novel approach to characterize SPB interactions with low molecular weight lipid-soluble substances. SPBs were formed on a silica-coated QCM-D crystal, exposed to various phenolic compounds (vanillin, gallic acid, and protocatechualdehyde), and subjected to linear temperature variation. While the exposure of the SPBs to the phenolic compounds did not result in detectable mass density changes, we observed noticeable alterations in their gel-fluid phase transitions. It was found that QCM-D can detect small variations in a SPB's main transition temperature (≪1 °C) and further resolve compound-specific lipid interactions. The acoustic sensing technique thus offers great potential for the use of supported membranes as stable and versatile model systems to study the transport of lipid-soluble substances into phospholipid bilayers and to assess their interactions therein.