Speaker
Description
Sprouting angiogenesis is the process by which new blood vessels form through the emergence of multicellular sprouts led by endothelial tip cells and followed by stalk cells. Tip–stalk selection is largely regulated by Delta–Notch signalling, involving Notch receptors and the ligands Delta and Jagged. Delta–Notch interactions can occur within the same cell (cis), leading to mutual degradation of Notch and Delta, or between neighbouring cells (trans), which suppresses Delta production in the receiving cell via lateral inhibition. This feedback can generate contrasting cellular states, characterised by high Delta/low Notch (tip-like) or low Delta/high Notch (stalk-like) profiles.
We investigate how lateral inhibition interacts with blood-flow-induced Delta/Notch ligand polarisation \cite{Mack2017} in a rearranging endothelial monolayer. We employ a multi–phase-field model \cite{gouveiaphd, nonomura_pf} coupled to Delta–Notch–Jagged dynamics \cite{boareto2015jagged}, enabling endothelial cell rearrangement together with phenotype regulation. Our simulations indicate that flow-driven ligand polarisation, when coupled to endothelial cell neighbour exchanges, substantially modulates the emergent signalling patterns and can bias tip–stalk outcomes. These results suggest that mechanical cues mediated by flow, together with lateral inhibition, are key determinants of endothelial phenotype at the onset of sprout evolution.
Bibliography
@article{Mack2017,
title={NOTCH1 is a mechanosensor in adult arteries},
author={Mack, Julia J and Mosqueiro, Thiago S and Archer, Brian J and Jones, William M and Sunshine, Hannah and Faas, Guido C and Briot, Anais and Arag{\'o}n, Raquel L and Su, Trent and Romay, Milagros C and others},
journal={Nature communications},
volume={8},
number={1},
pages={1620},
year={2017},
publisher={Nature Publishing Group UK London}
}
@article{boareto2015jagged,
title={Jagged--Delta asymmetry in Notch signaling can give rise to a Sender/Receiver hybrid phenotype},
author={Boareto, Marcelo and Jolly, Mohit Kumar and Lu, Mingyang and Onuchic, Jos{\'e} N and Clementi, Cecilia and Ben-Jacob, Eshel},
journal={Proceedings of the National Academy of Sciences},
volume={112},
number={5},
pages={E402--E409},
year={2015},
publisher={National Academy of Sciences}
}
@phdthesis{gouveiaphd,
title={Modelling Endothelial Cell's Collective Movement and Keratin Cytoskeleton Dynamics Using the Phase Field Method},
author={do Carmo Gouveia, Marcos Jo{\~a}o},
year={2023},
school={Universidade de Coimbra (Portugal)}
}
@article{Nonomura_pf,
title={Study on multicellular systems using a phase field model},
author={Nonomura, Makiko},
journal={PloS one},
volume={7},
number={4},
pages={e33501},
year={2012},
publisher={Public Library of Science San Francisco, USA}
}
