As a new form of regulated cell death, ferroptosis is closely related to various diseases. To interpret this biological behavior and monitor related pathological processes, it is necessary to develop appropriate detection strategies and tools. Considering that ferroptosis is featured with remarkable lipid peroxidation of various cell membranes, it is logical to detect membranes’ structural and environmental changes for the direct assessment of ferroptosis. For this sake, we designed novel polarity-sensitive fluorescent probes Mem-C₁C₁₈ and Mem-C₁₈C₁₈, which have superior plasma membrane anchorage, high brightness, and sensitive responses to environmental polarity by changing their fluorescence lifetimes. Mem-C₁C₁₈ with much less tendency to aggregate than Mem-C₁₈C₁₈ outperformed the latter in high resolution fluorescence labeling of artificial vesicle membranes and plasma membranes of live cells. Thus, Mem-C₁C₁₈ was selected to monitor plasma membranes damaged along ferroptosis process for the first time, in combination with the technique of fluorescence lifetime imaging (FLIM). After treating HeLa cells with Erastin, a typical ferroptosis inducer, the mean fluorescence lifetime of Mem-C₁C₁₈ displayed a considerable increase from 3.00 to 4.93 ns, with a 64% increase (corresponding to the polarity parameter Δf increased from 0.213 to 0.232). Therefore, our idea to utilize a probe to quantitate the changes in polarity of plasma membranes proves to be an effective method in the evaluation of the ferroptosis process.

中文翻译：

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极性敏感和膜特异性探针通过荧光寿命成像定量监测铁死亡

作为一种新的受调控的细胞死亡形式，铁死亡与多种疾病密切相关。为了解释这种生物学行为并监测相关的病理过程，有必要制定适当的检测策略和工具。考虑到铁死亡以各种细胞膜的显着脂质过氧化为特征，检测细胞膜的结构和环境变化以直接评估铁死亡是合乎逻辑的。为此，我们设计了新型极性敏感荧光探针Mem-C ₁ C ₁₈和Mem-C ₁₈ C ₁₈，它们具有优异的质膜锚定性、高亮度以及通过改变荧光寿命对环境极性的敏感响应。与Mem-C ₁₈ C ₁₈相比，Mem -C ₁ C ₁₈的聚集倾向要小得多，在人工囊泡膜和活细胞质膜的高分辨率荧光标记方面表现优于后者。因此，首次选择Mem-C ₁ C _{18结合荧光寿命成像（FLIM）技术监测沿铁死亡过程受损的质膜。}用典型的铁死亡诱导剂 Erastin 处理 HeLa 细胞后，Mem-C ₁ C _{18的平均荧光寿命}显示从 3.00 到 4.93 ns 的显着增加，增加了 64%（对应于极性参数Δf从 0.213 增加到 0.232）。因此，我们利用探针定量质膜极性变化的想法被证明是评估铁死亡过程的有效方法。