Open access microfluidic device for the study of cell migration during chemotaxis

Abstract

Cells sense and interpret chemical gradients, and respond by localized responses that lead to directed migration. An open microfluidic device (OMD) was developed to provide quantitative information on both the gradient and morphological changes that occurred as cells crawled through various microfabricated channels. This device overcame problems that many current devices have been plagued with, such as complicated cell loading, media evaporation and channel blockage by air bubbles. We used a micropipette to set up stable gradients formed by passive diffusion and thus avoided confounding cellular responses produced by shear forces. Two versions of the OMD are reported here: one device that has channels with widths of 6, 8, 10 and 12 μm, while the other has two large 100 μm channels to minimize cellular interaction with lateral walls. These experiments compared the migration rates and qualitative behavior of Dictyostelium discoideum cells responding to measurable cAMP and folic acid gradients in small and large channels. We report on the influence that polarity has on a cell's ability to migrate when confined in a channel. Polarized cells that migrated to cAMP were significantly faster than the unpolarized cells that crawled toward folic acid. Unpolarized cells in wide channels often strayed off course, yet migrated faster than unpolarized cells in confined channels. Cells in channels farthest from the micropipette migrated through the channels at rates similar to cells in channels with higher concentrations, suggesting that cell speed was independent of mean concentration. Lastly, it was found that the polarized cells could easily change migration direction even when only the leading edge of the cell was exposed to a lateral gradient.