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The role of the extracellular matrix as a memory hub to coordinate collective cell behaviour during vascular growth

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MMVW04 - Modelling non-Markov Movement Processes

I will discuss angiogenesis, the process where new blood vessels sprout from existing vasculature, crucial in development, wound healing, and the progression of numerous pathologies like cancer. While current mathematical models often adopt a leader-follower framework to study cell behaviour during angiogenesis, a closer look at endothelial cell dynamics reveals a more complex pattern: cells actively exchange positions within sprouts, challenging the conventional modelling approaches. We investigate how vascular sprouts maintain structural integrity amidst this dynamic cell behaviour. Our research emphasises the vital role of the extracellular matrix (ECM) in coordinating sprout growth. Through an agent-based model of early vascular growth, we integrate cell rearrangements and their interaction with the surrounding matrix. Our model accurately replicates vascular integrity by incorporating ECM remodelling during cell migration. Notably, this remodelled ECM serves as a memory hub, effectively coordinating blood vessel growth. Moreover, since the intensity of cell-ECM interaction depends on subcellular signalling, we also demonstrate that individual behaviour of endothelial cells from different cell lines (with impaired signalling) can be transmitted through ECM remodelling to obtain different morphologies in the resulting vasculature. This perspective offers new insights into angiogenesis and analogous biological systems, stressing ECM ’s essential role in guiding cellular movement. This is a joint work with Tomás Alarcón, Helen M. Byrne and Philip K. Maini. 

This talk is part of the Isaac Newton Institute Seminar Series series.

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