A chick embryo folds itself into a bird, a Hydra grows a new tentacle, and a tumour invades healthy tissue—all driven by the same physical forces that physicists are now learning to describe. This project builds computer models that treat living tissues as "active matter," a class of materials that constantly consume energy to push and pull themselves into shape. The gap it fills is fundamental: biologists know that forces and flows matter in development and disease, but they lack a unified physical theory to explain how cells collectively organise, remodel, and grow. By extending theories from active-matter physics, the researcher will simulate how confinement by the extracellular matrix controls cell spheroids and organoids, and how topological defects—like those seen in Hydra tentacles—might drive cancer metastasis. This is curiosity-driven fundamental science with no immediate practical application. However, similar work in active matter has already inspired soft robotics and self-healing materials. A deeper understanding of how tissues self-organise could eventually lead to better organoid engineering, improved cancer diagnostics, or new ways to control tissue regeneration.
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Changes in shape, and the reorganisation, differentiation and growth of cells and tissues that underpin them, are fundamental to biology. These are the processes by which a single cell develops into the diversity of living creatures. It is now well recognised that the physical concepts of stresses, forces and flows are an integral but little understood contribution to how biological systems self-organise by undergoing complex, yet surprisingly robust cell re-modelling and morphogenesis. For example, flows are intimately associated with invagination in the chick embryo, forces and confinement by the extracellular matrix appear to control the growth of cell spheroids and organoids, and topological defects have been implicated in the growth of Hydra tentacles and in cancer metastasis. Active matter describes materials that operate out of thermodynamic equilibrium, taking energy from their surroundings and using it to do work. This description is immediately applicable to living systems, and the recent development in the physics community of theories of active matter provide an unprecedented opportunity to understand the physical processes that drive mechanobiology and developmental processes. Guided by biological questions, I will extend and apply the theories of active matter physics, developing both cell-scale and continuum in silico models. My aim is to identify generic physical ideas that underpin collective cell motility, cell remodelling and tissue growth, the importance of confinement by the extracellular matrix and mechanochemical coupling. These investigations will combine to explain when and how forces and flows contribute to biological processes. The research will both contribute to a framework for the interdisciplinary toolkit that is necessary to understand biological self-organisation across scales and provide insight into the theories of active systems operating out of thermodynamic equilibrium.
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