Tipping the Balance: Robustness of Tip Cell Selection, Migration and Fusion in Angiogenesis
Figure 1
Overview of the spring-agent model.
(A) An endothelial cell is represented by a cylindrical, single layer square lattice mesh of agents, connected by springs, the physical properties for which follow Hookes Law. At either end (adjacent cells not shown) specialised junction springs and agents (pink) connect the cell to its neighbour cells along the vessel. (B) The underlying pathways modelled. VEGF activates VEGFR-2 receptors leading to both upregulation of Dll4 ligands and activation of actin polymerisation. Actin-based filopodia create positive feedback by increasing the cells surface area and aiding migration up the VEGF gradient, resulting in increased VEGF exposure. Dll4 binds to Notch receptors on neighbouring cells generating negative feedback by down regulating VEGFR-2 receptors. (C) To grow a filopodia a new agent and spring are created, see text for more details. When a filopodia spring exceeds the threshold length () a new node is inserted half way along the spring. It is given state ‘shaft’ and a focal adhesion. The original spring/s are deleted and new ones are created to reconnect the agents. Upon insertion of new nodes a spring connecting the top node back to the next node is also created. This is needed if the filopodia top node begins to retract. (D) As the filopodia extends shaft adhesions are created at regular intervals.