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Microfluidic device for studying cell migration in single or co-existing chemical gradients and electric fields

机译:用于研究单个或同时存在的化学梯度和电场中的细胞迁移的微流体装置

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摘要

Cell migration is involved in physiological processes such as wound healing, host defense, and cancer metastasis. The movement of various cell types can be directed by chemical gradients (i.e., chemotaxis). In addition to chemotaxis, many cell types can respond to direct current electric fields (dcEF) by migrating to either the cathode or the anode of the field (i.e., electrotaxis). In tissues, physiological chemical gradients and dcEF can potentially co-exist and the two guiding mechanisms may direct cell migration in a coordinated manner. Recently, microfluidic devices that can precisely configure chemical gradients or dcEF have been increasingly developed and used for chemotaxis and electrotaxis studies. However, a microfluidic device that can configure controlled co-existing chemical gradients and dcEF that would allow quantitative cell migration analysis in complex electrochemical guiding environments is not available. In this study, we developed a polydimethylsiloxane-based microfluidic device that can generate better controlled single or co-existing chemical gradients and dcEF. Using this device, we showed chemotactic migration of T cells toward a chemokine CCL19 gradient or electrotactic migration toward the cathode of an applied dcEF. Furthermore, T cells migrated more strongly toward the cathode of a dcEF in the presence of a competing CCL19 gradient, suggesting the higher electrotactic attraction. Taken together, the developed microfluidic device offers a new experimental tool for studying chemical and electrical guidance for cell migration, and our current results with T cells provide interesting new insights of immune cell migration in complex guiding environments.
机译:细胞迁移涉及生理过程,例如伤口愈合,宿主防御和癌症转移。各种细胞类型的运动可以通过化学梯度(即趋化性)来指导。除了趋化性外,许多细胞类型还可以通过迁移到电场的阴极或阳极(即电轴)来响应直流电场(dcEF)。在组织中,生理化学梯度和dcEF可能共存,并且两种指导机制可以协调方式指导细胞迁​​移。近年来,可以精确配置化学梯度或dcEF的微流体设备得到了越来越多的开发,并用于趋化性和电趋向性研究。但是,无法配置可控制的共存化学梯度和dcEF(允许在复杂的电化学引导环境中进行定量细胞迁移分析)的微流体装置。在这项研究中,我们开发了一种基于聚二甲基硅氧烷的微流体装置,该装置可产生更好的可控单一或共存化学梯度和dcEF。使用该设备,我们显示了T细胞趋化趋化因子CCL19梯度的趋化迁移或趋向于所施加dcEF阴极的趋化迁移。此外,在竞争性CCL19梯度存在的情况下,T细胞向dcEF阴极的迁移更强烈,表明较高的电吸引性。综上所述,开发的微流体装置为研究细胞迁移的化学和电学指导提供了一种新的实验工具,而我们目前对T细胞的研究结果为在复杂的指导环境中免疫细胞的迁移提供了有趣的新见解。

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