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。这是一个单细胞发展成生物多样性的过程。现在人们已经充分认识到，应力、力和流的物理概念是生物系统如何通过复杂的、但令人惊讶的强大的细胞重塑和形态发生进行自我组织的一个整体，但很少被理解。例如，流动与鸡胚内陷密切相关，细胞外基质的力和约束似乎控制细胞球体和类器官的生长，拓扑缺陷与九头蛇触手的生长和癌症转移有关。活性物质描述的是脱离热力学平衡的物质，它们从周围环境中获取能量并利用它做功。这种描述可以立即应用于生命系统，最近物理界在活性物质理论方面的发展为理解驱动机械生物学和发育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学理论，开发细胞尺度和连续体的硅模型。我的目标是确定支持集体细胞运动、细胞重塑和组织生长、细胞外基质和机械化学耦合限制的重要性的一般物理思想。这些调查将结合起来解释力和流何时以及如何促进生物过程。这项研究将有助于跨学科工具包的框架，这是理解跨尺度生物自组织所必需的，并提供对热力学平衡外活动系统运行理论的见解。

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.