Neutrophil chemotaxis in linear and complex gradients of interleukin-8 formed in a microfabricated device
Neutrophil chemotaxis in linear and complex gradients of interleukin-8 formed in a microfabricated device
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DOI：
10.1038/nbt712
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发表时间：
2002-08-01
影响因子：
46.9
通讯作者：
Toner, M
中科院分区：
文献类型：
--
作者：
Jeon, NL;Baskaran, H;Toner, M
尽管在过去的40年里积累了大量关于趋化性的知识，但由于研究人员无法立即生成简单的线性梯度并将其维持在稳定状态，这些研究受到了阻碍。在这里，我们描述了一种由软光刻微制造的装置，该装置由微流体通道网络组成，可以产生空间和时间控制的趋化因子梯度。当人类中性粒细胞定位在微通道内时，可以测试它们在简单和复杂的白细胞介素-8 （IL-8）梯度中的迁移。细胞表现出强烈的定向迁移，以线性梯度增加IL-8浓度。当细胞遇到趋化剂浓度突然下降到零（“悬崖”梯度）时，中性粒细胞的迁移突然停止。然而，当中性粒细胞受到化学引诱剂逐渐增加和减少（“山丘”梯度）的挑战时，细胞穿过最大浓度的峰值并在逆转方向之前进一步迁移。本文描述的技术提供了一种强大的方法来研究迁移细胞在各种条件下无法通过早期技术进行研究。
Although a wealth of knowledge about chemotaxis has accumulated in the past 40 years, these studies have been hampered by the inability of researchers to generate simple linear gradients instantaneously and to maintain them at steady state. Here we describe a device microfabricated by soft lithography and consisting of a network of microfluidic channels that can generate spatially and temporally controlled gradients of chemotactic factors. When human neutrophils are positioned within a microchannel, their migration in simple and complex interleukin-8 (IL-8) gradients can be tested. The cells exhibit strong directional migration toward increasing concentrations of IL-8 in linear gradients. Neutrophil migration halts abruptly when cells encounter a sudden drop in the chemoattractant concentration to zero ("cliff" gradient). When neutrophils are challenged with a gradual increase and decrease in chemoattractant ("hill" gradient), however, the cells traverse the crest of maximum concentration and migrate further before reversing direction. The technique described in this paper provides a robust method to investigate migratory cells under a variety of conditions not accessible to study by earlier techniques.