Figure 4.
High throughput mechanobiological screens for blocking load-induced enhancement of cancer cells to endothelial cells under shear stress. (A) Diagram of experimental protocol. The cells are loaded in the presence of compounds from a kinase inhibitor library and then the adhesion to inflamed endothelial cells under flow is measured. (B) Heat map of the adhesion and detachment of cancer cells with treatment with kinase inhibitors. (C) Example graphs from the kinase screen for a PI3K inhibitor and Jak3 inhibitor. (D) Results of the kinase inhibitor screen. Compounds in the lower left portion of the graph have reduced initial adhesion or τ50 to endothelial cells. The τ50 is an index of the strength of adhesion. It is the shear stress needed to cause detachment of 50% of the cells calculated from a curve fit to the detachment of the cells under increases shear stress.