Neutrophil chemotaxis in linear and complex gradients of interleukin-8 formed in a microfabricated device

• Published in: Nature biotechnology Vol. 20; no. 8; pp. 826 - 830
• Main Authors: Toner, Mehmet, Li Jeon, Noo, Baskaran, Harihara, Dertinger, Stephan K. W, Whitesides, George M, Van De Water, Livingston
• Format: Journal Article
• Language: English
• Published: New York, NY Nature 01.08.2002; Nature Publishing Group
• Subjects: Biological and medical sciences; Biological Assay - instrumentation; Biological Assay - methods; Biotechnology; Cancer; Cell Culture Techniques - instrumentation; Cell physiology; Chemotactic Factors - pharmacology; Chemotaxis, Leukocyte - drug effects; Cliffs; Cytokines; Dose-Response Relationship, Drug; Equipment Design; Fundamental and applied biological sciences. Psychology; Interleukin-8 - pharmacology; Lithography; Medical research; Microchemistry; Miniaturization; Molecular and cellular biology; Motility and taxis; Neutrophils; Neutrophils - cytology; Neutrophils - drug effects; Reynolds number; Gradient; Neutrophil; Chemotaxis; Interleukin 8; Cytokine; Microequipment
• ISSN: 1087-0156; 1546-1696
• DOI: 10.1038/nbt712

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.