The role of membrane active compounds in alteration of the lipid bilayer properties gives us more insight into their mechanistic pathway of entrance into the cells. We used an antidepressant, fluoxetine and two known environmental pollutants, the PFAS (per and poly fluoroalkyl substances), perfluorooctane sulfonate (PFOS), and perfluorooctanoic acid (PFOA) because of their high hydrophobicity and lipophilicity. These compounds play a significant impact on human health. We used a biophysical experimental setup known as planar lipid bilayer method to test the membrane activity of these compounds using a cation selective ion channel known as gramicidin A (Gr A) as the membrane probe. The method detects the change of membrane current as a function of the change of rate of flow of ions through a single ion channel and also measures how long the channel is open (lifetime). As previous studies have reported the presence of membrane activity in all of these compounds, we used different combinations of E. coli inner membrane lipids (phosphoethanolamine, cardiolipin, and phosphoglycerol) and conducted single channel electrophysiological measurements. We found that fluoxetine leads to an increase of GrA lifetime and decrease of GrA current in all the lipids. The reduction of GrA current is accounted to the probable electrostatic repulsion of the cations near the membrane surface. The possible alteration of hydrophobic properties of the lipid bilayers such as compressibility, thickness, curvature may have led an increase of GrA lifetime. However, the PFAs didn’t show any change with regards to the current but the lifetime did increase suggesting that the compounds somehow became embedded into the bilayer without being much responsive to the charge near membrane surface. All these results shed more light into how different hydrophobic properties alter the lipid bilayer properties.
Sen et al. (Sun,) studied this question.