CAREER: Nano-Plasmon Ruler Imaging for Direct Visualization of How Cells "Talk"

免疫系统由许多类型的细胞组成，这些细胞保护身体免受疾病的侵害。测量这些免疫细胞如何相互交流对于理解免疫反应很重要。目前，还没有可用的工具可以实时测量和跟踪免疫细胞分泌的化学信号。拟议的研究将通过建立基于工程纳米材料的成像系统来应对这一挑战。该奖项支持的研究人员将开发一种新型生物传感器，直接研究免疫细胞如何通过化学信号相互“交谈”。该项目在免疫通讯方面获得的新知识将有助于推进免疫疾病筛查和诊断技术。作为该奖项的一部分开发的新教育经验将培训K-12，本科生和研究生关于生物工程和纳米技术。将举办学习活动和公共活动，以提高公众对材料科学和生物技术的兴趣。细胞间的生化通讯通过细胞分泌的信号分子发生。免疫细胞之间的通讯是复杂和短暂的。测量信号事件的时间和空间分布对于理解免疫应答至关重要;然而，目前的方法是有限的，在静态和准静态条件下测量靶生物标志物。这个NSF CAREER项目的目标是通过直接实时绘制单个免疫细胞的多种细胞因子分泌来了解免疫细胞因子的通讯。为了实现这一点，金纳米粒子和DNA适体为基础的纳米等离子体标尺生物传感器将被开发。将探讨所需纳米材料的理化性质和组装参数，并指导传感器的制造。模型T细胞系将与模型树突状细胞、B淋巴细胞和中性粒细胞共培养，细胞对之间的串扰将在刺激细胞因子释放后直接成像。该奖项反映了NSF的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。

The immune system consists of many types of cells that defend the body against disease. Measuring how these immune cells communicate with each other is important for understanding immune response. Currently, there are no available tools that can measure and track chemical signals secreted by immune cells in real-time. The proposed research will address this challenge by establishing an imaging system based on engineered nanomaterials. The investigators supported by this award will develop a novel biosensor to directly study how immune cells “talk” to each other via chemical signals. The new knowledge gained by this project in immune communication will help advance immune disease screening and diagnosis technologies. New education experiences developed as part of this award will train K-12, undergraduate and graduate students about bioengineering and nanotechnology. Learning activities and public events will be performed to increase the public interests in material science and biotechnology.Intercellular biochemical communication occurs via cell-secreted signaling molecules. Communication between immune cells is complex and transient. Measuring the timing and spatial distribution of signaling events is critical to understanding immune response; however, current methodologies are limited, measuring target biomarkers under static and quasi-static conditions. The goal of this NSF CAREER project is to understand immune cytokine communication via direct real-time mapping of multiple cytokine secretion from individual immune cells. To accomplish this, a gold nano-particle and DNA aptamer based nanoplasmon ruler biosensor will be developed. Parameters governing the physiochemical properties and assembly of required nanomaterials will be explored and guide the fabrication of the sensor. Model T-cell lines will be co-cultured with model dendritic cells, B lymphocytes, and neutrophils and cross-talk between cell pairs will be directly imaged following stimulation of cytokine release.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.