Simulations of tumor tissue with metabolism, diffusion and fluctuating low blood flow with long flow stops.

Maximal ATP hydrolysis 100 µM/s. In the second (“Glycolytic capacity 100%”) and penultimate (“FBP buffering uncoupled” ) worksheet all cells had the full glycolytic capacity of tumor cells. In the rest of the simulations, 95% of cell volume is occupied by tumor cells with glycolytic capacity at 100% of tumor cell level. A second cell type with lower glycolytic capacity occupies the remaining 5% of cell volume. Simulation for 8 tissue layers of width 5 μm, resulting in a maximal diffusion distance of 40 µm. Result is given for the tissue layer at 15-20 μm from the blood vessel. Blood flow is constant for t≤0 and starts to fluctuate sinusoidally at t=0, periodically stopping fully for ~2 min; for t ≤ 0: blood flow = offset; for t>0: blood flow = offset - amplitude ∙ sin(2πt/Tperiod). offset = 2.2 ml/l intracellular H2O/s, amplitude = 3.5 ml/l/s, flow ≥ 0. Six different simulations with different glycolytic capacities in the second cell type are given. Worksheet “Glycolytic capacity 100%”: all cells 100% of tumor cell level; worksheet “Glycolytic capacity 50%”: Second cell type: glycolytic capacity 50% of tumor cell level; worksheet “Glycolytic capacity 30%”: Second cell type: glycolytic capacity 30% of tumor cell level; worksheet “Glycolytic capacity 10%”: Second cell type: glycolytic capacity 10% of tumor cell level; worksheet “Glycolytic capacity 1.5%”: Second cell type: glycolytic capacity 1.5% of tumor cell level; worksheet “FBP buffering uncoupled”: Glycolytic ATP synthesis depending on falling stores of fructose 1,6-biphosphate (FBP) and other GPI uncoupled, glycolytic capacity 100% of tumor level for all cells; worksheet “Parameters”: the parameters representing the glycolytic capacities in the simulations above.