Activated T lymphocytes migrate toward the cathode of DC electric fields in microfluidic devices

Abstract

Immune cell migration is a fundamental process that enables immunosurveillance and immune responses. Understanding the mechanism of immune cell migration is not only of importance to the biology of cells, but also has high relevance to cell trafficking mediated physiological processes and diseases such as embryogenesis, wound healing, autoimmune diseases and cancers. In addition to the well-known chemical concentration gradient based guiding mechanism (i.e. chemotaxis), recent studies have shown that lymphocytes can respond to applied physiologically relevant direct current (DC) electric fields by migrating toward the cathode of the fields (i.e. electrotaxis) in both in vitro and in vivo settings. In the present study, we employed two microfluidic devices allowing controlled application of electric fields inside the microfluidic channel for quantitative studies of lymphocyte electrotaxis in vitro at the single cell level. The first device is fabricated by soft-lithography and the second device is made in glass with integrated on-chip electrodes. Using both devices, we for the first time showed that anti-CD3/CD28 antibodies activated human blood T cells migrate to the cathode of the applied DC electric field. This finding is consistent with previous electrotaxis studies on other lymphocyte subsets suggesting electrotaxis is a novel guiding mechanism for immune cell migration. Furthermore, the characteristics of electrotaxis and chemotaxis of activated T cells in PDMS microfluidic devices are compared.

Electrotaxis of lung cancer cells in ordered three-dimensional scaffolds

“…[4][5][6] To illustrate the underlying mechanism, many in vitro experiments have been performed to study the electrotaxis of various cell types in response to dcEFs with a magnitude of a few tens to hundreds of mV/mm, similar to that experienced in vivo (e.g., at human skin wounds). Many cells include lymphocytes, 7,8 cancer cells, 9,10 leukemia cells, 3 and stem cells 11 were demonstrated to show evident electrotaxis effect. Some cells move toward the anode, [12][13][14] and others migrate toward the cathode.…”

“…7,8 Though 2D electrotaxis experiment is easy and convenient to carry out in the aspects of manipulation and observation, it may fail to capture some in vivo conditions where cells are situated in 3D microenvironment. The effect of the electric field may be different in cell movement over three-dimensional (3D) topology compared with 2D flat substrates.…”

“…Some cells move toward the anode, [12][13][14] and others migrate toward the cathode. 8,[15][16][17] Especially, a physiological dcEF originating from differential distribution of ion channels on polarized cells forms the so-called transepithelial potentials (TEP) which is reported to relate to the metastasis of cancerous tissues. 18,19 However, the underlying mechanism of such correlation still requires further investigation to be clear.…”

“…1932-1058/2012/6(1)/014102/14/$30.00 V C 2012 American Institute of Physics 6, 014102-1 microfluidic chips, [7][8][9] with dcEFs been applied via agar salt bridges 3,9,20 or platinum electrodes. 7,8 Though 2D electrotaxis experiment is easy and convenient to carry out in the aspects of manipulation and observation, it may fail to capture some in vivo conditions where cells are situated in 3D microenvironment.…”

Modulating chemotaxis of lung cancer cells by using electric fields in a microfluidic device

“…[12][13][14][15][16][17] There have also been a number of microfluidic devices used in the investigation of cell electrotaxis and other responses to dcEFs. 5,9,[18][19][20][21][22][23] It is therefore straightforward to combine the concentration gradients and dcEFs into a single device for quantitative comparisons between the influences of these two stimulations on cancer cell migration. However, because the requirements in the fluidic fields for stable concentration gradients and dcEFs could be different, careful design of the microfluidic channels would be needed for such studies on multiple cues of cell guidance.…”