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.
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The work was supported through funding from the National Institutes of Health R01GM122855 (SHW), and National Science Foundation (NSF) CMMI-1351162 (RLH), and National Science Foundation Graduate Research Fellowship 2016207025 (PAL).
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NSF CMMI-1351162 (RLH), NIH R01GM122855 (SHW), NSF GRFP 2016207025 (PAL).
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10237_2021_1442_MOESM1_ESM.gif
Multicellular vessel growth simulation. Movie illustrates the cell front and back positions during vessel growth with end stalk cell mitosis. Cell nodes are indicated by blue markers at the front nodes and red markers for the rear nodes. The tip cell is indicated by the blue lines while stalk cells are indicated by green lines. Junctions are indicated by red lines between cells, or black lines between the end stalk cell and the parent vessel wall. (GIF 8597 KB)
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Link, P.A., Heise, R.L. & Weinberg, S.H. Cellular mitosis predicts vessel stability in a mechanochemical model of sprouting angiogenesis. Biomech Model Mechanobiol 20, 1195–1208 (2021). https://doi.org/10.1007/s10237-021-01442-8
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DOI: https://doi.org/10.1007/s10237-021-01442-8