Figure 6

Spatial organization in a compartmental model of 3D microtumors. (A) Compartments of a 3D microtumor model include an outer layer that separates an inner layer and core of tumor cells from the extracellular compartment. A decreasing gradient of nutrients in models 1 and 2 (M1 and M2, respectively) is formed through nutrient consumption and diffusion between the outer layer, inner layer, and core of the microtumor. M2 also considers a gradient of stress signals that are strongest at the microtumor core. (B) Schematic diagram of the transport of nutrients (n) and their consumption for the expression of proliferative genes associated with Ki-67⁺ status (‘Ki67’), the rate-limiting enzyme for serine biosynthesis (PHGDH), and a molecule that inhibits expression of PHGDH (Inh). Expression of Inh is omitted in M1. Extracellular, outer layer, inner layer, and core compartments are noted in subscripts (e, i, o, and c respectively). (C) The abundance of nutrients, ‘Ki67′, and PHGDH in each of the microtumor compartments for M1 (top) and M2 (bottom). Each quantity is normalized to its abundance in the outer layer compartment.