Simulations of tumor tissue including fluctuating blood flow, diffusion and tumor cell metabolism.

ATP hydrolysis is high initially and strongly reduced when energy status is compromised. Simulation for tissue with a maximal diffusion distance of 40 µm. Result for the tissue layer at 15-20 μm from the blood vessel is given. Blood flow is constant for t≤0 and starts to fluctuate sinusoidally at t=0, periodically reaching zero for a moment, but not fully stopping. For t ≤ 0: blood flow = offset. For t>0: blood flow = offset - amplitude ∙ sin(2πt/Tperiod). offset = 4.4 ml/l intracellular H2O/s, amplitude = 4.4 ml/l/s, flow ≥ 0. Worksheet A. Simulations of tumor cells (100% of cell volume at 100% of the glycolytic capacity). From 3505-3550 sec the contribution to ATP synthesis in the tail part of glycolysis derived from falling stores of fructose 1,6-biphosphate (FBP) and other GPI is uncoupled and therefore not contributing to total ATP synthesis. Worksheet B. Simulations of tumor cells (80% of cell volume) and a second cell type with 10% of tumor glycolytic capacity (20% of volume) in tissue with fluctuating blood flow. Worksheet C. Simulations of tumor cells (80% of cell volume) and a second cell type with 1.5% of tumor glycolytic capacity (20% of volume) in tissue with fluctuating blood flow. See Supplementary Text for details.