BIOPHYSICAL MECHANISMS OF CHEMOTAXIS

趋化性的生物物理机制

• 批准号: 8364134
• 负责人: ALEXANDER VAN OUDENAARDEN
• 金额: $ 2.23万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-06-01 至 2012-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8364134
• 关键词: Amoeba genus; Biological Models; Biomedical Research; Cells; Chemicals; Chemotactic Factors; Chemotaxis; Cyclic AMP; Dictyostelium; Dictyostelium discoideum; Embryonic Development; Eukaryotic Cell; Funding; Grant; Immune response; Individuality; Lasers; Measures; Microfluidic Microchips; National Center for Research Resources; Noise; Physiologic pulse; Play; Population; Principal Investigator; Research; Research Infrastructure; Resources; Signal Transduction; Source; Techniques; United States National Institutes of Health; Wound Healing; angiogenesis; cost; lithography; research study; response; social

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Chemotaxis, the ability of the cell to sense and move in the direction of higher concentration of chemicals, is an integral part of immune response. Additionally it plays a key role in wound healing, angiogenesis, and embryogenesis. Dictyostelium discoideum, a model system for eukaryotic cells, is a social amoeba and has been studied extensively over the past twenty years. In our experiments, we probe and quantitatively measure the initial chemotactic response of single Dictyostelium cells by quantifying the localization dynamics of this key component of signaling transduction network in response to repeated spatio-temporal pulses of chemoattractant. We find that the response of a single cell is very reproducible from pulse-to-pulse. In contrast, we observe a large variability in the chemotactic response from cell-to-cell even when different cells in population are exposed to the same pulse. Although on average a population of cells finds the correct direction of the pulse, a significant variability is observed in the direction and the magnitude of the response. Origins of the noise and cell individuality by quantitatively are explored by measuring the external concentration of the cAMP molecules. We observe that the reliability in the directional sensing mechanism is not limited by the low number of external cAMP molecules and the noise does not decrease when the external cAMP molecules increases by 2 orders of magnitude. Additional studies aimed at better understanding the chemotaxis mechanism will utilize microfluidic devices produced via soft lithography techniques to generate a variety of spatio-temporal chemical gradients.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 趋化性是细胞感知化学物质浓度较高并朝更高浓度化学物质方向移动的能力，是免疫反应的一个组成部分。此外，它在伤口愈合、血管生成和胚胎发生中发挥着关键作用。盘基网柄菌是真核细胞的模型系统，是一种社会性变形虫，在过去二十年中得到了广泛的研究。在我们的实验中，我们通过量化信号转导网络关键组成部分响应趋化剂重复时空脉冲的定位动态，探测并定量测量单个盘基网柄菌细胞的初始趋化反应。我们发现单个细胞的反应在脉冲与脉冲之间具有很强的可重复性。相比之下，我们观察到即使群体中的不同细胞暴露于相同的脉冲，细胞间的趋化反应也存在很大的差异。尽管平均而言，细胞群找到了正确的脉冲方向，但在响应的方向和幅度上观察到显着的变化。通过测量 cAMP 分子的外部浓度，定量探索噪声和细胞个性的起源。我们观察到，定向传感机制的可靠性不受外部 cAMP 分子数量较少的限制，并且当外部 cAMP 分子增加 2 个数量级时，噪声不会降低。旨在更好地理解趋化机制的其他研究将利用通过软光刻技术生产的微流体装置来产生各种时空化学梯度。