Real time analysis of cancer ovarian cell growth and migration on soft surfaces

It is well established that the nano-geometry and mechanical properties of a material's interface can significantly influence - and potentially enhance - cell adhesion, growth, proliferation, and migration, collectively referred to as cell behavior. At the same time, these behavioral responses are inherently dependent on the cell's own biological characteristics, including its type, age, cell cycle phase, and whether it is normal or cancerous - as well as, in the latter case, the stage of cancer. In this context, we hypothesize that these material and cellular factors may act synergistically, such that carefully engineered materials can modulate and amplify cellular responses. Specifically, such materials may function as amplifiers, accentuating the behavioral differences between distinct cell lines and thereby improving our ability to distinguish between them. Here, we used this concept to segregate OVCAR-429 ovarian cancer cells silenced for the EXT1 gene (shEXT1) from a control (SCR): i.e. cells infected with an empty lentivirus. EXT1 encodes a glycosyltransferase implicated in the synthesis of heparan sulfate proteoglycans and may play a role in cancer cell invasion and metastasis. We produced polydimethylsiloxane (PDMS) substrates with low values of Young's modulus in the MPa range, and moderate values of roughness of about $20\mathrm{nm}$. Then, we monitored cell-behavior over time on PDMS substrates and on standard rigid microplates for comparison. Analysis of cell trajectories revealed that shEXT1 cells exhibited significantly reduced motility on PDMS surfaces compared control cells, with cell velocity and diffusivity reduced by more than twofold, whereas no significant differences were observed on standard surfaces. Our results thus indicate the potential of soft biomaterials to reveal biological differences in disease models.