Zoloft changes the shape of red blood cells in accordance with the bilayer couple model

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The Perlstein lab generated these unpublished images of red blood cells treated with different concentrations of the the SSRI antidepressant sertraline/Zoloft®, which is a cationic amphipath.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.

双层偶联模型（bilayer couple model）由Singer与Sheetz于1974年在其标志性论文《生物膜作为双层偶联体：药物-红细胞相互作用的分子机制》（原英文标题："Biological Membranes as Bilayer Couples. A Molecular Mechanism of Drug-Erythrocyte Interactions."）中提出。该模型指出，带电分子会在脂质双分子层（lipid bilayer）中发生不对称积累。这类药物-膜相互作用可在红细胞中被直观观测到，因红细胞恰好仅具备一层外侧脂质双分子层。

佩尔斯坦实验室（Perlstein lab）制备了这批未发表的图像，展示了经不同浓度SSRI类抗抑郁药舍曲林（sertraline，商品名Zoloft®）处理后的红细胞。舍曲林属于阳离子两亲性分子（cationic amphipath），其会在红细胞质膜的内层单分子层中积累，引发质膜向内弯曲，最终形成杯状结构。杯状结构的形成程度与舍曲林浓度呈正相关，浓度范围从个位数微摩尔直至引发膜裂解的临界浓度。

无需担忧，服用该药物的人群体内Zoloft®的血清浓度极低，因此人体红细胞状态完好。