Pstalk and Ptip are length changes of the tip cell due to stalk cell proliferation and tip cell proliferation, respectively. Elongation Estalk and proliferation Pstalk of the stalk cells occur independently and separately, i. e, they do not occur in the same timestep. The specific Cases 1 and 2 refer to when the adjacent stalk cell segment elongates, but the stalk cells do not proliferate and Tanespimycin when see Appendix 2 in Additional file 1. Joining Another Sprout or Vessel Anastomoses, or the connection of a growing sprout to another vessel occurs when the leading node of the tip cell touches an adjacent vessel or another tip cell node, randomly. This is a first implementation, and subse quently activation of the adjacent vessel may be a requirement for joining of the tip cell.

In this initial model, anastomoses occur infrequently. there is no restriction on sprout movement by surrounding tissue or a bias from interstitial fluid flow. Effects of Dll4 The presence of Dll4 has an effect on those rules involving tip cell formation, tip cell Inhibitors,Modulators,Libraries proliferation, Inhibitors,Modulators,Libraries and branching probability. Experimentally, the observed tip cell number in Dll4 vasculature is near 1. 4 times that of control tip cell number. A two fold Inhibitors,Modulators,Libraries difference was used in the model to allow integer number of tip cells, when observing only a few capillaries. Note also that the number of tip cells formed from an existing capillary versus a new capillary formed by angiogenesis is expected to differ. More tip cell formation and branching is hypothesized in the newly formed vessel.

Model Parameters Table 2 lists the parameters in the model, with their relevant references. Table S1 Inhibitors,Modulators,Libraries provides initial values of all variables used in the computer code. Table S2 provides parameter estimates for cell velocity, as found from in vitro 2D and 3D experiments. Velocity values found from Table S1 were used in part to determine migration rules. Parameters were obtained for endothelial cells where possible. Where a non endothe lial cell type is used, this estimate is stated explicitly. Ranges are given for endothelial cell dimensions in parentheses, and the default values used for this model are presented. The value ranges include sizes for mammalian cells, in different tissues. The current model estimates cell and vessel sizes for three dimen sional in vitro conditions, using human umbilical vein endothelial cells. When the model is applied to a specific species and tissue, during certain Inhibitors,Modulators,Libraries vascular conditions, the dimensions will be specified for this environment Cisplatin alone. Platform The model was programmed in Java, using Suns Java3D and MASON libraries. The JAVA IDE used was Borland JBuilder. Output of the Java code was written into TecPlot, additional results were written to text files.