Cellular mitosis predicts vessel stability in a mechanochemical model of sprouting angiogenesis

Abstract

Angiogenesis, the formation of new vessels, occurs in both developmental and pathological contexts. Prior research has investigated vessel formation to identify cellular phenotypes and dynamics associated with angiogenic disease. One major family of proteins involved in angiogenesis are the Rho GTPases, which govern function related to cellular elongation, migration, and proliferation. Using a mechanochemical model coupling Rho GTPase activity and cellular and intercellular mechanics, we investigate the role of cellular mitosis on sprouting angiogenesis. Mitosis-GTPase synchronization was not a strong predictor of GTPase and thus vessel signaling instability, whereas the location of mitotic events was predicted to alter GTPase cycling instabilities. Our model predicts that middle stalk cells undergoing mitosis introduce irregular dynamics in GTPase cycling and may provide a source of aberrant angiogenesis. We also find that cellular and junctional tension exhibit spatial heterogeneity through the vessel, and that tension feedback, specifically in stalk cells, tends to increase the maximum forces generated in the vessel.