Program
| Poster PS30A | |
|---|---|
| Nicholas Flann | |
| Utah State University | |
| Title | Lateral Inhibition coordinates endothelial stalk-tip cell type transitions during sprouting angiogenesis to produce self-symmetric vessel networks |
| Abstract | Angiogenesis, the development of new blood vessels from existing vessels, is critical in wound repair, tissue development and the progression of many important diseases including cancer. Under normal conditions in sprouting angiogenesis, the growing vessel network extends along a frontier distal to the existing vessel and forms a regular self-symmetric pattern of lumina. Many mechanisms are known to contribute to the correct formation of the new vessel network such as Vegf signaling and activation, adherens junctions, basement membrane restructuring, and endothelial tip cell chemotaxis and haptotaxis, but their coordination and interaction are poorly understood. This poster reports on a modeling study using an extended Glazier-Graner-Hogeweg Model, (GGH) that implements a high fidelity simulation of sprouting angiogenesis. The GGH is detailed enough so that individual endothelial cells have shape and extend over space and time. Sprout formation and anastomosis are not modeled explicitly, but emerge from the independent behavior of each cell. Cell mechanisms include those listed above and growth, adhesion, extracellular matrix (ECM) fiber adhesion and degradation, and filopodia extension and retraction. Protein signaling and regulation are represented as ODEs and capture critical behaviors such as VegF secretion, diffusion through tissue, and uptake and activation by endothelial cells. This poster studies the role of internal signaling cascades and membrane signaling in coordinating the spatial and temporal behavior of the endothelial cells during sprouting angiogenesis. Endothelial cells in the growing vessels are known to change their type from stalk to tip, and from tip to stalk using some form of VegF activated Notch-based lateral inhibition. Since the two types of endothelial cells have distinct cell properties (e.g. proliferation, adhesion, growth, chemotactic sensitivity, proteases secretion), changing the specific pattern of type transitions produces distinct vessel morphologies. The study implements a plausible set of signaling networks and type transition rules (that map protein expression levels to type transitions) then evaluates the regularity of the resulting vessel network. In particular, measures of vessel network connectedness and self symmetry are computed from the simulated tissue morphology. Results show that membrane signaling appears to be critical in constructing regular vessel networks. |
| Coauthors | Gregory Podgorski |
| Location | Woodward Lobby (Monday-Tuesday) |