In the current model, the voxel associated datastructure contains infor mation on local kinase inhibitor Trichostatin A concentrations of growth factors. Representation of Cells Each preexisting capillary vessel is composed of four endothelial cells. Endothelial cells are represented as a series of segments that occupy a cylindrical volume specified by a radius and length. Segments are defined by two connected nodes. Each node is associated with a voxel, and serves as a position used to calculate the local environment of a cell segment. An activated tip cell is defined throughout the simulation by one segment that can vary in length, as the cell changes position, grows or elongates. Stalk cells are represented by one activated segment adjacent to the tip cell and by any number of nonadjacent, quiescent segments.

As the adjacent stalk cells change position and shape, their segments can change in number and radius, and the activated segment closest to the Inhibitors,Modulators,Libraries tip cell can change in length and radius. Endothelial cells on the preexisting capillaries have a static length and radius, throughout a model run. Local VEGF Levels VEGF gradient, ?, and Inhibitors,Modulators,Libraries local VEGF concentrations, are inputs into the current model and remain constant for every run of the simulation. This condition can be relaxed by coupling the cell model to previously developed VEGF models. For graphs and model runs presented here, there is Inhibitors,Modulators,Libraries either no gradient, or the ? is defined as in Appendix 1, where noted. Rules Behavioral rules based on biophysical properties and experimental observations govern the activation and move ment of endothelial cells in the model.

Table 3 lists the main rules governing endothelial cell migration and proliferation, and the related experimental references. To represent biological mechanisms in the model and perform these rules, the computer code implements over 80 logical statements at each timestep, for each active cell segment. At Inhibitors,Modulators,Libraries the beginning of each run of Inhibitors,Modulators,Libraries the simulation, Boolean rules are defined. These rules determine proliferation, Cell Activation In experiments of angiogenic sprouting, a single cell is initially shown to branch out in a spindle shaped fashion from an existing vessel. This tapered Ponatinib TNKS1 sprout tip is a highly polarized cell, which expresses genes differently than adjacent stalk cells, including higher levels of VEGFR2 and PDGFb. The tip cell also proliferates with a much lower probability than stalk cells. Cells in an existing blood vessel can be activated by a threshold increase in VEGF protein levels. One cell migration and elongation. see Table 4. At the start of any sequence of rules for tip or stalk cell segment movement, the values of these global Booleans dictate whether or not a certain event is permitted.