Cell volume regulation - the search for a volume sensor

细胞体积调节——寻找体积传感器

• 批准号: RGPIN-2018-05075
• 负责人: Grygorczyk, Ryszard
• 金额: $ 2.4万
• 依托单位: Université de Montréal
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2018
• 资助国家: 加拿大
• 起止时间: 2018-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=652545
• 关键词: Cell; volume; regulation; search; sensor

Animal cell volume is a critical factor for normal cell function and survival. Cells change their volume in many physiological and pathological conditions, such as brain injuries, diabetic complications and other disorders. Cell volume is tightly regulated via accumulation or loss of intracellular ions and other osmotically active substances. However, a major gap exists in our knowledge of how cells detect volume perturbations and how they trigger volume compensatory mechanisms. The long term objective of the proposed research program is to elucidate volume-sensing mechanism(s) in animal cells. To achieve this goal we will use novel method previously developed in our laboratory which allows imaging single, live cells in 3 dimensions and simultaneous measurements of cell volume and intracellular calcium. In the proposed research program we will further improve cell imaging system to allow simultaneous measurements of volume-dependent release of adenosine triphosphate (ATP). Extracellular ATP acts as an important molecule for inter-cellular signaling and we will determine its role in triggering volume regulatory mechanisms. Using molecular viscometers (so called molecular rotors) we will also examine role of volume-dependent viscosity changes of cytoplasm in cell volume regulation. For these experiments, we have already developed in collaboration with our colleagues at the University of North Texas suitable prototype fluorescent molecular viscometers and obtained encouraging results. Based on the data we are confident to accomplish the proposed research goals. ***This research program will provide both innovation in single-cell imaging techniques and notable advancement of our understanding of cell volume sensing, but also will provide opportunity for training of graduate and undergraduate students. Exploration of the volume-sensing mechanisms is essential for full understanding of a broad range of related cellular processes in normal and pathological conditions. Thus, the outcomes of this program will benefit not only research community in the field of cell volume regulation but also those interested in cell physiology and biology in general. The nature of this research program encompassing cell physiology and electrophysiology, hydrogel biophysics, microscopy imaging, chemistry, mechanical design and software development, will allow us to train students in a multidisciplinary manner.

动物细胞体积是正常细胞功能和存活的关键因素。细胞在许多生理和病理条件下改变其体积，例如脑损伤，糖尿病并发症和其他疾病。细胞体积通过细胞内离子和其他药理活性物质的积累或损失来严格调节。然而，一个主要的差距存在于我们的知识，细胞如何检测体积扰动，以及它们如何触发音量补偿机制。该研究计划的长期目标是阐明动物细胞中的体积感知机制。为了实现这一目标，我们将使用我们实验室先前开发的新方法，该方法允许对单个活细胞进行三维成像，并同时测量细胞体积和细胞内钙。在拟议的研究计划中，我们将进一步改进细胞成像系统，以允许同时测量体积依赖性释放的三磷酸腺苷（ATP）。细胞外ATP作为细胞间信号传导的重要分子，我们将确定其在触发体积调节机制中的作用。使用分子粘度计（所谓的分子转子），我们还将研究细胞质的体积依赖性粘度变化在细胞体积调节中的作用。对于这些实验，我们已经与北德克萨斯大学的同事合作开发了合适的荧光分子粘度计原型，并获得了令人鼓舞的结果。基于这些数据，我们有信心完成所提出的研究目标。* 这项研究计划将提供单细胞成像技术的创新和我们对细胞体积传感的理解的显着进步，但也将为研究生和本科生的培训提供机会。体积感知机制的探索对于充分理解正常和病理条件下广泛的相关细胞过程至关重要。因此，该计划的成果不仅有利于细胞体积调节领域的研究界，也有利于那些对细胞生理学和生物学感兴趣的人。该研究计划的性质包括细胞生理学和电生理学，水凝胶生物物理学，显微成像，化学，机械设计和软件开发，将使我们能够以多学科的方式培养学生。