Figure 1

Schematics of Module-based Mulitscale Angiogenesis Modeling Methodology. A) Skeletal muscle angiogenesis is modeled as a multi-step process. It starts with a blood flow simulation followed by a simulation of oxygen convection-transport process. Using O₂ tissue distribution, VEGF secretion by myocytes is computed as a function of oxygen-dependent transcription factors HIF1α and PGC1α; then a VEGF reaction-transport process is computed. Lastly, capillary formation is simulated based on VEGF concentration and gradients. Feedback loops increase the complexity of the model since a new geometry with nascent vessels will affect blood flow conditions, tissue hypoxia, and VEGF secretion and distributions. All four processes are simulated using a variety of modeling techniques and languages. We use Java as the language for modeling the controller, and apply JNI plugins to link these modules together. The controller is composed of four sub-packages, including Process, Biosystems, IO and Exceptions. B) Communications between different modules and Java codes in core package are implemented by transferring each module into a shared object library (SO file in Linux). Upper panel shows that two wrapper files (includes Java-to-C and C-to-Fortran wrapper) are written to communicate between the flow Java class defined in the controller and the Fortran flow module, to call the flow module in Fortran. Lower panel shows that a JNI C wrapper is required to transfer the data between the modeling controller (in Java) and the Oxygen/VEGF module (in C/C++).