Physical Cues of the Extracellular Matrix Directs Invasion Phenotypes of Tumor Spheroids*

Solid tumors are known to remodel both the mechanics and alignment of their local extracellular matrix (ECM). As these tumors interact with the ECM, and as individual cells are invading, surrounding ECM fibers are radially aligned and create pathways for easier and more efficient cell invasion. As radially aligned fibers help facilitate invasion, tangentially aligned fibers can act as a barrier around the tumor that inhibits invasion. We use spheroids embedded in type 1 collagen gels as our tumor model to create a more physiologically relevant model for how tumors react to their environment. By changing the density, crosslinking, and alignment of the type 1 collagen gels, we create a spectrum of physical cues to measure the invasion profiles and morphodynamics of the tumor spheroids. We find that both the invasion profiles and morphodynamics are highly dependent on the stiffness, pore size, and alignment of the ECM.