BioMEMS Resource Center, Massachusetts General Hospital, Shriners Hospital for Children, and Harvard Medical School, Boston, MA 02129, USA.
Integr Biol (Camb). 2010 Nov;2(11-12):639-47. doi: 10.1039/c0ib00011f. Epub 2010 Aug 2.
The directional migration of human neutrophils in classical chemotaxis assays is often described as a "biased random walk" implying significant randomness in speed and directionality. However, these experiments are inconsistent with in vivo observations, where neutrophils can navigate effectively through complex tissue microenvironments towards their targets. Here, we demonstrate a novel biomimetic assay for neutrophil chemotaxis using enclosed microfluidic channels. Remarkably, under these enclosed conditions, neutrophils recapitulate the highly robust and efficient navigation observed in vivo. In straight channels, neutrophils undergo sustained, unidirectional motion towards a chemoattractant source. In more complex maze-like geometries, neutrophils are able to select the most direct route over 90% of the time. Finally, at symmetric bifurcations, neutrophils split their leading edge into two sections and a "tug of war" ensues. The competition between the two new leading edges is ultimately resolved by stochastic, symmetry-breaking behavior. This behavior is suggestive of directional decision-making localized at the leading edge and a signaling role played by the cellular cytoskeleton.
在经典趋化性测定中，人中性粒细胞的定向迁移常被描述为“偏向随机游走”，这意味着速度和方向性存在显著的随机性。然而，这些实验与体内观察结果不一致，在体内观察中，中性粒细胞可以有效地在复杂的组织微环境中导航并朝向其靶标。在这里，我们使用封闭的微流控通道展示了一种用于中性粒细胞趋化性的新型仿生测定法。值得注意的是，在这些封闭条件下，中性粒细胞再现了体内观察到的高度稳健和高效的导航。在直通道中，中性粒细胞朝着化学引诱剂源进行持续的单向运动。在更复杂的类迷宫几何形状中，中性粒细胞能够在 90%以上的时间内选择最直接的路线。最后，在对称分叉处，中性粒细胞将其前缘分为两部分，然后进行“拔河”。两个新前缘之间的竞争最终通过随机、打破对称的行为来解决。这种行为表明定向决策定位于前缘，并且细胞细胞骨架起着信号作用。
