Fig. 2.
Epithelial cell EGF-uptake changes the orientation bias at bifurcations. (a) Microscopy image of one MDA cell migrating past the channel junction (orange dot), from the cell compartment (blue dot) toward the outer compartment (green dot). The ratio between the lengths of the channels toward the outer compartment and the side chamber (yellow dot) was 3 : 1 for the device to the left and 1 : 1 for the device to the right. (b) Inversion of gradient slope toward the outer compartment and the side chamber due to cellular EGF uptake, for 3 : 1 length channel ratio and 1/2× EGF concentration in the side chamber. In the absence of cellular EGF uptake, a large positive gradient toward the outer compartment (green dot) and a negative gradient toward the side chamber (yellow dot) were predicted. When cellular EGF uptake is taken into consideration, the EGF concentration in the cell compartment decreases (blue dot) and a stronger gradient toward the side chamber compared to the one toward the outer compartment develops by the time a cell arrives at the junction (orange dot). (c and d) Bias of HMEC, HPC, and PC9 cells toward side chambers with various concentrations of EGF (1× in the outer compartment vs. 5×, 1×, 1/2×, 1/10× in the side chamber) and 1 : 1 ratio between the length of the channels after bifurcation, toward the outer compartment and the side chamber (c), or 3 : 1 ratio (d). Epithelial cells consistently migrate toward the higher concentration of EGF when the ratio of the two channels is 1 : 1. Cells can migrate toward a lower concentration of EGF (1/2×) when the side chamber is positioned closer to the bifurcation (3 : 1 length ratio), suggestive of significant EGF concentration decrease at the bifurcation. N represents the number of cells observed moving through the bifurcating channels, only the first cell reaching the bifurcation was analyzed.