Synthesis and Exploration of Highly Fluorescent Thiazolothiazole Molecular Sensors for Probing Membrane Potential Dynamics

用于探测膜电位动力学的高荧光噻唑并噻唑分子传感器的合成与探索

• 批准号: 10114747
• 负责人: Michael G. Walter
• 金额: $ 46.25万
• 依托单位: UNIVERSITY OF NORTH CAROLINA CHARLOTTE
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-15 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10114747
• 关键词: Address; Brain; Cell Membrane Structures; Cell membrane; Cell physiology; Cells; Cellular Membrane; Characteristics; Chicago; Collaborations; Communication; Complex; Development; Dyes; Electron Transport; Electronics; Electrons; Exhibits; Feedback; Fluorescence; Fluorescent Dyes; Future; Generations; Goals; Grant; Guidelines; Hela Cells; Image; Imaging Device; Imaging Techniques; Laboratories; Light; Membrane Potentials; Molecular; Molecular Structure; Neurobiology; Neurons; Outcomes Research; Oxidation-Reduction; Performance; Process; Property; Reaction; Reaction Time; Research; Research Personnel; Role; Signal Transduction; Spectrum Analysis; Stains; Structure; Students; System; Testing; Thiazoles; Thick; Time; Tissues; Training; Triplet Multiple Birth; Universities; Xenopus oocyte; benzothiazole; cytotoxicity; design; dipole moment; electric field; experience; functional group; graduate student; hands on research; improved; membrane activity; next generation; patch clamp; quantum; response; sensor; small molecule; tool; two-photon; undergraduate student; voltage; voltage sensitive dye

Project Abstract: The long-term goal of this project is to understand how highly fluorescent and photostable thiazolothiazole molecular sensors are impacted by changing electric fields in cellular membranes. Tracking the changes in cell membrane potential offers the potential to gain a deep understanding of complex and rapidly changing cellular physiology. This is especially true for mapping the coordinated activity of neurons in the brain. Fluorescent, small molecule voltage sensitive dyes (VSDs) have greatly impacted this field, however there is still a great need to develop new dyes with enhanced long wavelength emission for imaging in thick tissues, improved photostability for long-term imaging, and improved cell membrane voltage sensitivity. In this project, we propose the synthesis and exploration of a unique and highly fluorescent thiazolo[5,4-d]thiazole dye system. TTz dyes are the next generation of imaging tools because they exhibit high photochemical stability, are easy to prepare/modify, show fast response times, good cell membrane localization, negligible cytotoxicity, and are sensitive to cellular membrane potential. We will conduct spectroscopic and electrochemical characterizations to understand the role of various heterocyclic molecular structures on the cell membrane localization and voltage sensing. We will evaluate the voltage sensitivity performance of the dyes, which will provide important feedback for tuning the photophysical properties to enhance their cell membrane potential sensitivity.

项目摘要： 该项目的长期目标是了解如何高度荧光和 光稳定的噻唑并噻唑分子传感器受到改变的电 细胞膜中的电场跟踪细胞膜电位的变化 提供了深入了解复杂和快速 改变细胞生理学这对于绘制协调的 大脑中神经元的活动荧光，小分子电压敏感 染料（VSD）对这一领域产生了巨大的影响，但仍有很大的需求 开发具有增强的长波长发射的用于成像的新染料， 厚的组织，改善的长期成像的光稳定性，和改善的细胞 膜电压灵敏度在这个项目中，我们提出了合成和 探索独特的高荧光噻唑并[5，4-d]噻唑染料体系。 TTZ染料是下一代成像工具，因为它们表现出很高的成像性能。 光化学稳定性，易于制备/改性，显示快速响应时间， 良好的细胞膜定位，细胞毒性可忽略不计，并且对 细胞膜电位我们将进行光谱和电化学 表征，以了解各种杂环分子的作用 细胞膜上的结构定位和电压传感。我们将 评估染料的电压灵敏度性能，这将提供 重要的反馈，用于调整生物物理性质，以提高其细胞 膜电位敏感性。