他汀类药物是抑制胆固醇生物合成、预防心血管疾病和治疗高胆固醇血症的最广泛使用的药物之一。此外，他汀类药物还在各种疾病中表现出与胆固醇无关的益处，包括阿尔茨海默氏病的神经保护特性、冠状动脉疾病的抗炎作用以及癌症的抗增殖活性，这可能是由于他汀类药物的相互作用和脂质双层的改变所致。然而，他汀类药物的膜调节作用以及他汀类药物改变脂质双层的机制仍然知之甚少。在这项工作中，我们探讨了他汀类药物对模型脂质双层和活细胞的膜调节作用。通过使用荧光寿命成像显微镜（FLIM）与粘度敏感环境探针相结合，我们证明疏水性而非亲水性他汀类药物能够改变模型和活细胞膜中的微粘度和脂质顺序。此外，我们表明疏水性辛伐他汀能够形成纳米级富含胆固醇的结构域并使脂质双层中的胆固醇浓度均质化。我们的结果为理解辛伐他汀对脂质双层中胆固醇的脂质顺序和横向组织的双峰效应提供了一个机制框架。最后，我们证明辛伐他汀暂时降低活细胞质膜的微粘度，使其更具渗透性并增加细胞内化疗药物积累的水平。

Statins are among the most widely used drugs for the inhibition of cholesterol biosynthesis, prevention of cardiovascular diseases, and treatment of hypercholesterolemia. Additionally, statins also exhibit cholesterol-independent benefits in various diseases, including neuroprotective properties in Alzheimer's disease, anti-inflammatory effects in coronary artery disease, and antiproliferative activities in cancer, which likely result from the statins' interaction and alteration of lipid bilayers. However, the membrane-modulatory effects of statins and the mechanisms by which statins alter lipid bilayers remain poorly understood. In this work, we explore the membrane-modulating effects of statins on model lipid bilayers and live cells. Through the use of fluorescence lifetime imaging microscopy (FLIM) combined with viscosity-sensitive environmental probes, we demonstrate that hydrophobic, but not hydrophilic, statins are capable of changing the microviscosity and lipid order in model and live cell membranes. Furthermore, we show that hydrophobic simvastatin is capable of forming nanoscale cholesterol-rich domains and homogenizing the cholesterol concentrations in lipid bilayers. Our results provide a mechanistic framework for understanding the bimodal effects of simvastatin on the lipid order and the lateral organization of cholesterol in lipid bilayers. Finally, we demonstrate that simvastatin temporarily decreases the microviscosity of live cell plasma membranes, making them more permeable and increasing the level of intracellular chemotherapeutic drug accumulation.