A hybrid continuum-discrete modelling approach to predict and control angiogenesis: analysis of combinatorial growth factor and matrix effects on vessel-sprouting morphology.

Angiogenesis is crucial during many physiological processes and is influenced by various biochemical and biomechanical factors. Models have proved useful in understanding the mechanisms of angiogenesis and also the characteristics of the capillaries formed as part of the process. We have developed a three-dimensional hybrid, agent-field model where individual cells are modelled as sprout-forming agents in a matrix field. Cell independence, cell-cell communication and stochastic cell response are integral parts of the model. The model simulations incorporate probabilities of an individual cell to transition into one of four stages--quiescence, proliferation, migration and apoptosis. We demonstrate that several features, such as continuous sprouts, cell clustering and branching, that are observed in microfluidic experiments conducted under controlled conditions using few angiogenic factors can be reproduced by this model. We also identify the transition probabilities that result in specific sprout characteristics such as long continuous sprouts and specific branching patterns. Thus, this model can be used to cluster sprout morphology as a function of various influencing factors.