Ovarian cancer cells exhibit diverse migration strategies on stiff collagenous substrata

In homoeostasis, the shape of epithelial cells and their sessility, i.e. lack of movement are intricately linked together. Alterations in this relationship as a result of malignant transformation and variations, thereof by the mechanical microenvironments that cancer cells encounter as they migrate are as yet ill-understood. Here we explore the interdependency of such traits in two morphologically distinct but invasive ovarian cancer cell lines (OVCAR-3 and SK-OV-3) under mechanically variant contexts. To do so, we came up with a minimal metric toolkit consisting of velocity, local and global turning angles, persistence of migration, major axis dynamics, morphomigrational angle, and elongation dynamics, and rigorously measured their variation using a Shannon entropic distribution to map heterogeneity in behavior between, and across, trajectories of migration. Two stiffness conditions on polymerized Collagen I with Youngs moduli of 0.5 (soft) and 20 (stiff) kPa were chosen. Both the epithelioid OVCAR-3 and mesenchymal SK-OV-3 cells on soft substrata migrated slowly and in an undirected manner. On stiff substrata, SK-OV-3 showed a persistent directed motion with higher velocity. Surprisingly, OVCAR-3 cells on higher stiffness moved at a velocity higher than SK-OV-3 cells and showed a distinct angular motion. The polarity of SK-OV-3 cells on stiff substrata was well-correlated with their movement, whereas for OVCAR-3, we observed an unusual slip behavior, where the axes of cell shape and movement were poorly correlated. An examination of their deformability showed that OVCAR-3 and SKOV-3 on softer substrata were relatively rigid but showed greater shape variation (especially OVCAR-3) on stiffer substrata. Therefore, a rigorous quantification using the above metric toolkit reveals how an interplay between intrinsic deformability and the mechanical microenvironment on pathotypic matrix substrata allow distinct migratory dynamics of epithelioid and mesenchymal ovarian cancer cells.