A novel microfluidic platform for studying mammalian cell chemotaxis in different oxygen environments under zero-flow conditions

The cell's micro-environment plays an important role in various physiological and pathological phenomena. To better investigate in vivo cellular behaviors, researchers have expended great effort in building controlled in vitro biophysical and biochemical environments. Because a cell's gaseous environment affects properties such as its division, metastasis, and differentiation, we developed a zero-flow based platform for studying mammalian cell chemotaxis behavior in different oxygen environments. This platform can construct a linear range of oxygen tensions within one chip (i.e., from 1.4% to 3.6% or 5.5% to 14.5%). To study cell chemotaxis behavior under varying oxygen environments, the chemical gradient direction is established perpendicularly to oxygen change within an observation area. Because the observation area is not subject to flow, shear force is of no concern. In addition, water flow around the cell chambers greatly reduces evaporation and makes long-term microscope imaging possible. In this study, we precisely measure the chemotaxis velocity of MCF-7 human breast cancer cells under different oxygen tension conditions towards CXCL12, which is a stromal cell-derived factor. We find that cell migration rates are not equivalent, even under two close oxygen tensions. We also observed that cells move faster towards high concentrations of chemoattractant when the oxygen tension is below 3% due to the increased expression of HIF-1 (hypoxia-inducible factor 1), which promotes a transition to the amoeboid rather than mesenchymal mode of movement. Our experiments demonstrate that this new microfluidic platform is useful for the quantitative study of mammalian cell chemotaxis under different oxygen conditions in the absence of shear force. We also shed light on the study of chemotaxis under other gaseous environments.