This image combines in vitro and in silico demonstrations of environmental niches that drive phenotypic segregation in mixed metabolic phenotype spheroids. In vitro: Coculture of low glycolytic MCF7-GFP and high glycolytic MDA-MB-231-RFP as spheroids started with a random mixture of both cells and over time each cell line moved to their favorable habitat, MDA-MB-231 to the edge and MCF7 to the center. In silico: Simulation of a mathematical model of tumor cells with low (green) and high (red) glycolytic phenotypes, subject to a gradient of nutrients similar to a spheroid. The simulation was initialized with equal numbers of both cell types, well-mixed. Over time, the glycolytic phenotypes moved to the edge in the simulation. For details, see article by Ibrahim-Hashim and colleagues on page 2242.