 Dynamic remodeling of the extracellular matrix, ECM, is essential for development, wound healing, and normal organ homeostasis, but can lead to life-threatening pathological conditions when uncontrolled or excessive. Fibrotic diseases and cancer are examples of such conditions that arise due to ECM remodeling, accounting for over 45% of deaths in the developed world and over 90% of cancer deaths, respectively. Understanding and quantifying the impact of environmental cues provided by the ECM on disease progression is crucial for discovering novel therapeutic targets and treatment strategies. This requires appropriate in vitro and in vivo models to mimic disease and technologies that enable accurate monitoring, imaging, and quantification of the ECM. This article was authored by Thomas O'Cox and Janine T. Ehler.