Figure 1.

Illustration of the gap between single cell behavior in a homogeneous microfluidic environment and a ”real-world” tumor system. (a) Illustration of the competing upstream and downstream single cell behavior (essentially one-dimensional) in a homogeneous microfluidic setting as observed in Ref. 26. (b) Illustration of a real-world tumor setting where excessive IF fluid flow is generated from a leaky intratumoral vascular system and adsorbed by lymphatics in the peritumoral region. The IF flow away from the primary tumor may give rise to a downstream heterogeneous chemotactic migration towards higher chemokine concentrations in the peritumoral region whereas the upstream migration mechanism might be effective for higher volume fractions of tumor cells near the tumor margin. (c) Plot showing ${\widehat{f}}_{\text{c}}({\alpha }_{\text{c}})$ which is directly involved in the fluid stress-mediated cell velocity component in (1) with parameters as given by (11), (14), and (15). When we zoom in on ${\widehat{f}}_{\text{c}}$ we see that it has a tiny positive slope for small ${\alpha }_{\text{c}}$. This reflects a fine-tuned mechanotransductive machinery that will generate downstream migration of tumor cells for a sufficiently small cell volume fraction (${\alpha }_{\text{c}}\in (0,0.012)$), otherwise will create upstream cell migration.