Figure 12
Summary of the reported mechanosensing behavior of ovarian cancer cells. The top panel depicts cells (grey) adhered to a model microenvironment with a gradient of rigidity, increasing from left to right (depicted by the depth of blue shading and density of the blue ‘spring’ coils). Individual SKOV3 and highly metastatic SKOV3.ip1 cells adhere to FN-coated hydrogels of low rigidity but fail to spread or form focal adhesions or organized actin filaments. This is accompanied by low levels of phosphorylated myosin light chain (pMLC), low traction forces (upper panel, red ‘springs’), low cell motility, and nuclear exclusion of YAP1. Cells adhered to stiffer substrates show significantly increased focal adhesion formation, F-actin organization, and MLC phosphorylation, which reinforce each other and support increased cell spreading, cellular traction forces, and nuclear accumulation of YAP1. Also, globally-increased substrate stiffness supports higher levels of cell migration while directional increases in matrix tension promote directional durotaxis. These differences at the individual cell level are reflected at the level of multicellular spheroids, where disaggregation is enhanced by matrix stiffness through a mechanotransduction pathway involving ROCK, actomyosin contractility, and FAK. Some design elements of this schematic were inspired by Plotnikov & Waterman52.
