As part of a longstanding collaboration with Rex Gaskins (Illinois Animal Science), #harleylab’s Emily Chen describes the use of a three-dimensional hydrogel to study the impact of matrix composition and metabolic challenges on GBM cell invasion. The margins of glioblastoma tumors in the brain containing striking gradient in matrix stiffness and hypoxia, and in this paper just accepted in the journal Biomaterials Science we show combinations of these signals enhance GBM cell invasion and alter processes associated with matrix remodeling.