Tracking the Epithelial-Mesenchymal Transition in Engineered 3D Microenvironments
The epithelial-mesenchymal transition (EMT) is associated with tumor invasion and drug resistance but remains controversial due to several technology gaps. First, EMT is a rare and exceptional event that may be overlooked with population averages and endpoints. Second, EMT may be inappropriately biased in classical 2D monolayer culture, which lacks physiologically relevant cues, including 3D tissue architectures. Here, I present our recent results on precision measurement of EMT in space and time within engineered 3D microenvironments. We show that after EMT, cells in confined micropillar arrays display highly heterogeneous collective and individual migration behaviors. These emergent dynamics can be understood using a physical analogy with phase transitions during the solidification of binary alloys. We extend these technologies to 3D silk-collagen hydrogels, for comprehensive tracking of tumor organoid disorganization and dissemination. Finally, we describe new techniques for patterning microfluidic channels into these hydrogels in order to mimic the tumor microenvironment with controlled interstitial flows, gradients and forces.