Sensing Microsystems for Decoding Cellular Communications

来自加州大学戴维斯分校的亚历山大和高亚东获得了纳米生物传感计划的一项奖项的支持，以开发传感微系统，用于研究在有毒物质或感染损伤的情况下肝细胞之间的通信。 附近细胞之间的信号传导参与炎症反应，最终导致它们的损伤或死亡，但原因和影响仍然不确定。 这项工作是为了揭示在具有适当传感能力的芯片实验室环境中肝细胞之间信号传导的不同方面。 待开发的技术和设备预计将有利于解决生物学中需要解开的复杂细胞通信的其他问题，例如，创伤愈合、纤维化等。一批不同的本科生、研究生和博士后研究员正在接受该项目的培训。旁分泌信号在肝脏中特别相关，其中损伤触发了包括炎症和纤维化细胞因子/生长因子在内的旁分泌信号的复杂组合。最近的研究结果表明，在中毒或感染下，肝细胞可能不是基质细胞/巨噬细胞炎症信号的简单受害者，但可能是肝脏中信号传导的积极参与者和可能的触发者。对细胞通信的理解仍然有限，因为无法识别分泌信号何时何地出现以及它们如何影响邻近细胞的工具。该项目正在努力通过开发用于解剖细胞通信的新型生物传感器和微流体设备来满足这一需求。这些结合了多路适体传感器，用于并行检测几种细胞分泌的炎性细胞因子，以及利用阀门控制不同肝细胞类型在芯片上通信的方式和时间的可重构微流体。 有几个问题正在寻求技术解决方案：如何动态监测细胞分泌的因子？如何再生传感器以同时检测几种细胞分泌因子？当存在两种细胞类型时，如何识别起源和响应信号？在异型细胞通信期间分泌速率如何变化？这项工作旨在更深入地了解细胞和组织水平对肝脏疾病或损伤的反应，并确定治疗的细胞靶点和时间窗口。 由于局部微环境中的细胞相互作用在整个生物学中非常重要，因此正在开发的工具将广泛适用。

Alexander Revzin and Yadong Gao from the University of California Davis are supported by an award from the Nano-Biosensing Program to develop sensing microsystems for investigating the communication between liver cells in cases of injury by toxic substances or infection. Signaling between nearby cells is involved in inflammation responses and ultimately their damage or death, but there remains uncertainty of what is cause and what is effect. This work is to unravel the different aspects of signaling between liver cells in a laboratory-on-a-chip environment with appropriate sensing capabilities built in. The techniques and devices to be developed are expected to have benefits for other problems in biology with complex cellular communications that need to be unraveled, e.g., wound healing, fibrosis and so on. A diverse group of undergraduate and graduate students and post doctoral fellows are being trained in this project.Paracrine signaling is particularly relevant in the liver where an injury triggers a complex combination of paracrine signals including inflammatory and fibrogenic cytokines/growth factors. Recent findings suggest that, under toxication or infection, hepatocytes may not be simple victims of stromal-cell/macrophage inflammatory signals but may be active participants in and possibly triggers of the signaling in the liver. The understanding of cellular communications remains limited because the tools for discerning where and when secreted signals appear and how they affect neighboring cells are not available. This project is working to answer this need by developing novel biosensors and microfluidic devices for dissecting cellular communication. These incorporate multiplexed aptasensors for detection of several cell-secreted inflammatory cytokines in parallel as well as reconfigurable microfluidics utilizing valves to control how and when different liver cell types communicate on chip. There are several questions for which technological solutions are being sought: How may cell secreted factors be dynamically monitored? How may sensors be regenerated for simultaneous detection of several cell-secreted factors? How may originating and responding signals be recognized when two cell types are present? How do secretion rates change during heterotypic cellular communications? This work aims at deeper understanding of cell- and tissue-level responses to liver disease or injury and identification of cellular targets and temporal windows for treatment. Because cellular interactions in the local microenvironment are important throughout biology, the tools being developed will be widely applicable.