Directional decisions during neutrophil chemotaxis inside bifurcating channels
Directional decisions during neutrophil chemotaxis inside bifurcating channels
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DOI：
10.1039/c0ib00011f
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发表时间：
2010-01-01
影响因子：
2.5
通讯作者：
Irimia, Daniel
中科院分区：
文献类型：
--
作者：
Ambravaneswaran, Vijayakrishnan;Wong, Ian Y.;Irimia, Daniel
人类中性粒细胞在经典趋化测定中的定向迁移通常被描述为“偏见的随机行走”，这意味着速度和方向性的显着随机性。但是，这些实验与体内观察结果不一致，中性粒细胞可以有效地通过复杂的组织微环境导航到目标。在这里，我们展示了使用封闭的微流体通道进行中性粒细胞趋化性的新型仿生测定。值得注意的是，在这些封闭的条件下，中性粒细胞概括了体内观察到的高度健壮和有效的导航。在直接通道中，中性粒细胞向趋化剂源进行持续的单向运动。在更复杂的迷宫样几何形状中，中性粒细胞能够在90％的时间内选择最直接的路线。最后，在对称分叉时，中性粒细胞将其前缘分为两个部分，随之而来的是“拖船”。最终通过随机，对称性的行为解决了两个新的领先边缘之间的竞争。这种行为暗示了定向在前缘定位的定向决策以及细胞细胞骨架发挥的信号传导作用。
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.