ActBio: Exploiting the Parallels between Active Matter and Mechanobiology

形状的变化，以及支撑它们的细胞和组织的重组、分化和生长，是生物学的基础。这些都是单个细胞发育成生物多样性的过程。现在人们很好地认识到，应力、力和流动的物理概念是生物系统如何通过经历复杂但令人惊讶的强大细胞重新建模和形态发生而自组织的不可或缺的、但鲜为人知的贡献。例如，流动与鸡胚胎中的内陷密切相关，细胞外基质的力和限制似乎控制着细胞球体和有机体的生长，拓扑缺陷与九头蛇触须的生长和癌症转移有关。活性物质描述了在热力学平衡之外运行的材料，从周围环境中获取能量并利用它做功。这一描述立即适用于生命系统，而活动物质理论在物理学领域的最新发展为理解推动机械生物学和发展过程的物理过程提供了前所未有的机会。在生物学问题的指导下，我将扩展和应用活性物质物理的理论，在计算机模型中发展细胞尺度和连续统。我的目标是确定支持集体细胞运动、细胞重塑和组织生长的一般物理概念，以及细胞外基质限制和机械力化学耦合的重要性。这些研究将结合起来解释力量和流动何时以及如何对生物过程做出贡献。这项研究将有助于建立一个跨学科工具包的框架，这对于理解跨尺度的生物自组织是必要的，并提供对活动系统在热力学平衡之外运行的理论的洞察。

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.