Programmable dual-gel tumor-mimetic 3D culture platforms for studying effects of interstitial flow and transport coupling on cancer cell migration
Metastasis is responsible for the vast majority of cancer deaths. As the first step of metastasis, migration of tumor cells through the extracellular matrix (ECM) to the surrounding tissue is regulated by a variety of biochemical and biophysical signals in the ECM, which may even couple with each other to impose a combined effect. For example, interstitial flow—the slow convection of fluid occurring in the interstitial space of ECM—not only conjoins matrix permeability (or specific hydraulic conductivity) to provide direct mechanical cues to the resident cells through shear and normal stress, but also couples with biomolecular diffusion to induce chemotactic signals (e.g. CCR7-mediated autologous chemotaxis). Therefore, a mechanistic and quantitative understanding of the dependence of cancer cell migration on interstitial flow would require an ability to manipulate interstitial flow, matrix permeability, and bioactive molecules in the ECM without affecting other contributing factors such as stiffness and physical confinement.