Dual-gel Dual-porosity 3D ECM Mimics for Studying flow-induced mechanotransduction

Interstitial flow in the Extracellular Matrix (ECM) has been postulated to play a key role in regulating behaviors of cells. Among the cellular behaviors, cell migration is hypothesized to be influenced by interstitial flow via two mechanisms: autologous chemotaxis and integrin-mediated focal adhesion activation. It is commonly accepted that the effectiveness of the former depends on interstitial fluid velocity and the effectiveness of the latter depends on the flow-induced force on a cell, which relates to both interstitial fluid velocity and matrix permeability. The two mechanisms have never been rigorously verified using the traditional single hydrogel-based models due to the inevitable correlation between matrix permeability and stiffness. In this work, we developed a dual-gel dual-porosity 3D ECM mimics to address this challenge. With the new model, one can individually control the interstitial flow and matrix permeability without affecting the primary matrix stiffness. We also conduct preliminary studies on the efficiency of our model in studying the effect of interstitial flow on cancer cell migration.