FIGURE 1.

Schematic depicting the contribution of various physical cues during different steps of the metastatic cascade. In the primary tumor, cancer cells experience mechanical compression and hydraulic pressure as well as different levels of substrate stiffness, viscoelasticity and extracellular fluid viscosity. Following primary tumor cell dissemination, invading cancer cells encounter substrate stiffness and viscoelasticity, mechanical compression, fluid viscosity, solid barriers, confined tracks, and other topographies within the local tissue microenvironment. During intravasation, cancer cells experience shear stress caused by blood flow and continue to be exposed to this physical cue while in circulation. The viscosity of blood is also elevated relative to interstitial fluids, which potentially impacts cell behavior. As cancer cells arrest to the vascular endothelium and extravasate out of the bloodstream, they experience shear stress from the blood flow. Taken together, cancer cells are exposed to many different physical forces during the metastatic cascade which they must sense, integrate and interpret to engage appropriate cellular mechanisms for efficient dissemination. Schematic created with BioRender.com.