The bilayer couple model in action
The bilayer couple model was proposed in 1974 by Singer and Sheetz in their landmark paper: “Biological Membranes as Bilayer Couples. A Molecular Mechanism of Drug-Erythrocyte Interactions.” The bilayer couple model states that charged molecules accumulate asymmetrically in lipid bilayer. This drug-membrane interaction can be easily visualized in red blood cells, which conveniently have a single outer lipid bilayer.
The Perlstein lab generated these unpublished images of red blood cells treated with different concentrations of the the SSRI antidepressant sertraline/Zoloft®, which is a cationic amphipath. Sertraline accumulated in the inner monolayer of the red blood cell plasma membrane, causing the plasma membrane to curve inward, culminating in cup formation. The degree of cup formation is proportional to sertraline concentration, beginning at single-digit micromolar concentrations up to a critical concentration at which membrane lysis occurs.
Don’t worry. The extremely low serum concentration of Zoloft in people taking the drug means that your red blood cells are just fine.