State Key Laboratory of Chemo/Biosensing and Chemometrics, Hunan Provincial Key Laboratory of Biomacromolecular Chemical Biology, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, P. R. China.
College of Biology, Hunan University, Changsha 410082, P. R. China.
Anal Chem. 2020 Nov 17;92(22):15194-15201. doi: 10.1021/acs.analchem.0c03764. Epub 2020 Nov 2.
Neurotransmitters are essential chemical mediators for neuronal communication in variable neuromodulations. However, the progress of neuroscience is hampered by the shortage of suitable sensors to track neurotransmitters with high spatial and temporal resolution. Here, we introduce a self-assembled DNA-nanoprism fluorescent probe capable of nongenetically engineering the cell surface for ultrasensitive imaging of the neurotransmitter release at a single live-cell level. The DNA-nanoprism structure conjugated with three cholesterol tails enables the probe to rapidly and stably anchor on the cell surface within 10 min. The detection of neurotransmitters is achieved by equipping the DNA-nanoprism with an aptamer-based "turn-on" fluorescent sensory module for the transmitter of interest. In a proof-of-concept study, we directly visualized the transient dopamine (DA) release on the cell surface with selective responsivity and high spatiotemporal precision and further explored the dynamic correlation between DA release and calcium influx triggered by high K. This study provides a robust and sensitive tool for cell-surface-targeted imaging of neuromodulations, which might open up a new avenue to improve the understanding of neurochemistry and advance neuroscience research.
神经递质是变异性神经调制中神经元通讯的重要化学介质。然而，神经科学的进展受到缺乏合适的传感器的限制，这些传感器无法以高时空分辨率跟踪神经递质。在这里，我们介绍了一种自组装的 DNA-纳米棱镜荧光探针，能够非遗传工程化细胞表面，用于在单个活细胞水平上对神经递质释放进行超灵敏成像。与三个胆固醇尾巴连接的 DNA-纳米棱镜结构使探针能够在 10 分钟内快速而稳定地锚定在细胞表面。通过为感兴趣的递质配备基于适体的“开启”荧光感应模块，实现了对神经递质的检测。在概念验证研究中，我们直接可视化了细胞表面上具有选择性响应和高时空精度的瞬态多巴胺 (DA) 释放，并进一步探讨了 DA 释放与高 K 触发的钙内流之间的动态相关性。这项研究为针对神经调制的细胞表面靶向成像提供了一种强大而灵敏的工具，这可能为改善神经化学理解和推进神经科学研究开辟新途径。
