Speaker Roeland Merks (CWI) talks about modelling blood vessel growth and the role of contact-inhibited chemotaxis.

Location: CWI, room M279

Modelling de novo and sprouting blood vessel growth: role of contact-inhibited chemotaxis

Blood vessels form either when dispersed endothelial cells (the cells lining the inner walls of fully-formed blood vessels) organize into a vessel network (vasculogenesis), or by sprouting or splitting of existing blood vessels (angiogenesis). Although these mechanisms are closely related biologically, no current model explains both phenomena with a single biophysical mechanism. Most computational models describe sprouting at the level of the blood vessel, ignoring how cell behavior drives branch splitting during sprouting.

We present a cell-based simulation based on plausible behaviors of endothelial cells. The endothelial cells secrete a chemoattractant, which attracts other endothelial cells. As in the classic Keller-Segel model, chemotaxis causes cells to aggregate into isolated clusters. However, adding adhesion-driven contact inhibition of chemotaxis causes cells to organize into networks and cell aggregates to sprout, reproducing aspects of both de novo and sprouting blood-vessel growth. We discuss two branching instabilities responsible for our results.

Cells at the surface of the cell clusters attempting to migrate to the center of the clusters, produce a buckling-type instability. In a model variant that eliminates the surface normal force, a dissipative mechanism drives sprouting, with the secreted chemical acting both as a chemoattrant and as an inhibitor of pseudopod extension. The branching instabilities responsible for our results, which result from contact inhibition of chemotaxis, are both generic developmental mechanisms and interesting examples of unusual types of patterning instabilities.

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