Yang Ke, Wu Jiandong, Xu Guoqing, Xie Dongxue, Peretz-Soroka Hagit, Santos Susy, Alexander Murray, Zhu Ling, Zhang Michael, Liu Yong, Lin Francis
Institute of Applied Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui, P. R. China.
Integr Biol (Camb). 2017 Apr 18;9(4):303-312. doi: 10.1039/c7ib00037e.
Chemotaxis is a classic mechanism for guiding cell migration and an important topic in both fundamental cell biology and health sciences. Neutrophils are a widely used model to study eukaryotic cell migration and neutrophil chemotaxis itself can lead to protective or harmful immune actions to the body. While much has been learnt from past research about how neutrophils effectively navigate through a chemoattractant gradient, many interesting questions remain unclear. For example, while it is tempting to model neutrophil chemotaxis using the well-established biased random walk theory, the experimental proof was challenged by the cell's highly persistent migrating nature. A special experimental design is required to test the key predictions from the random walk model. Another question that has interested the cell migration community for decades concerns the existence of chemotactic memory and its underlying mechanism. Although chemotactic memory has been suggested in various studies, a clear quantitative experimental demonstration will improve our understanding of the migratory memory effect. Motivated by these questions, we developed a microfluidic cell migration assay (so-called dual-docking chip or D-Chip) that can test both the biased random walk model and the memory effect for neutrophil chemotaxis on a single chip enabled by multi-region gradient generation and dual-region cell alignment. Our results provide experimental support for the biased random walk model and chemotactic memory for neutrophil chemotaxis. Quantitative data analyses provide new insights into neutrophil chemotaxis and memory by making connections to entropic disorder, cell morphology and oscillating migratory response.
趋化性是引导细胞迁移的经典机制，也是基础细胞生物学和健康科学中的一个重要课题。中性粒细胞是研究真核细胞迁移的广泛使用的模型，中性粒细胞趋化性本身可对机体产生保护性或有害性免疫作用。尽管过去的研究已经让我们对中性粒细胞如何有效地在趋化因子梯度中导航有了很多了解，但许多有趣的问题仍然不清楚。例如，虽然用成熟的有偏随机游走理论来模拟中性粒细胞趋化性很诱人，但实验证据受到了细胞高度持续迁移特性的挑战。需要一种特殊的实验设计来检验随机游走模型的关键预测。几十年来一直引起细胞迁移领域关注的另一个问题是趋化记忆的存在及其潜在机制。尽管在各种研究中都有人提出趋化记忆，但清晰的定量实验证明将增进我们对迁移记忆效应的理解。受这些问题的启发，我们开发了一种微流控细胞迁移分析方法（即所谓的双对接芯片或D芯片），该方法能够在一块芯片上通过多区域梯度生成和双区域细胞排列来同时测试中性粒细胞趋化性的有偏随机游走模型和记忆效应。我们的结果为中性粒细胞趋化性的有偏随机游走模型和趋化记忆提供了实验支持。定量数据分析通过将熵无序、细胞形态和振荡迁移反应联系起来，为中性粒细胞趋化性和记忆提供了新的见解。
