We study how the structure and mechanics of the cellular microenvironment guide fundamental processes like migration, proliferation, and extracellular matrix (ECM) synthesis. To explore these interactions, we create synthetic biomaterials that mimic the 3D, fibrous nature of stromal or interstitial tissues and combine them with advanced molecular tools, live imaging, and microfabrication techniques. These approaches enable us to model cell-ECM interactions in diseases like cancer and fibrosis and leverage material cues to direct cell function for tissue engineering and regenerative medicine.