State Key Laboratory of Medicinal Chemical Biology, Frontiers Science Centre for New Organic Matter, Tianjin Key Laboratory of Biosensing and Molecular Recognition, Research Centre for Analytical Sciences, College of Chemistry and School of Medicine, Nankai University, Tianjin 300071, P. R. China.
Qingdao Academy of Agricultural Sciences, Qingdao 266100, P. R. China.
Bioconjug Chem. 2022 Nov 16;33(11):2076-2087. doi: 10.1021/acs.bioconjchem.2c00469. Epub 2022 Oct 25.
Lipid molecules contribute to a large extent to the regulation of cellular signaling, as cellular signals are generated primarily through the selective interaction of various cellular proteins with lipids in the plasma membrane. Hence the location, concentration, and duration of lipids on the cell membrane are critical for the selection of proteins and the initiation of signaling. To monitor the concentration and location of lipid molecules on the cell membrane, researchers have developed a variety of lipid biosensors that allow quantitative visualization of lipid molecules in living cells based on lipid-binding domains with high specificity, sensitivity, and biocompatibility, providing a powerful tool for the study of cellular signaling mechanisms involving lipid molecules. In this review, we first introduced the emergence of lipid-binding domains and then focused on the practical considerations on how to implement the lipid sensor, including probe selection, modification, characterization, and imaging techniques. We then described experimental observables and the relevant physicochemical parameters in the context of single-molecule studies in cells. Finally, we presented our views on the future development of lipid sensors and methods for lipid quantification.
脂质分子在很大程度上有助于细胞信号转导的调节，因为细胞信号主要是通过各种细胞蛋白与质膜中的脂质的选择性相互作用产生的。因此，细胞膜上脂质的位置、浓度和持续时间对于蛋白质的选择和信号的启动至关重要。为了监测细胞膜上脂质分子的浓度和位置，研究人员开发了多种脂质生物传感器，这些传感器基于具有高特异性、灵敏度和生物相容性的脂质结合域，允许对活细胞中的脂质分子进行定量可视化，为涉及脂质分子的细胞信号转导机制的研究提供了有力的工具。在这篇综述中，我们首先介绍了脂质结合域的出现，然后重点介绍了如何实施脂质传感器的实际考虑因素，包括探针选择、修饰、表征和成像技术。然后，我们在细胞中单分子研究的背景下描述了实验可观察量和相关物理化学参数。最后，我们提出了我们对脂质传感器未来发展和脂质定量方法的看法。
