Mechanistic mixture models of mechanics of morphogenesis with murine measurement

描述（由申请人提供）： 目标：生命世界嵌入到物理世界中。小有机体生活在一个扩散的世界中。我们其他人需要一个管道系统来运输我们生活所需的所有材料。肺、肾、乳腺和许多其他器官中都存在分支导管系统。该项目的主要目标是了解创建分支系统的组织动力学机制。它还旨在阐明使用形态发生的连续力学模型的最佳方法，以真实地描述发育组织中的力学和运输。此外，该项目将为具有接口的混合模型开发新的数值方法。然后，我们将在实时活分支系统（早期胚胎肺）中测试这些模型。 目标 1：开发准确、稳定、高效的方法来解决具有尖锐界面的混合问题。 目标 2：开发一套分支上皮机械方面的模型。 目标 3：确定分支上皮内部力学的形态发生效应。 目标 4：确定分支上皮外部力学的形态发生效应。 该项目的一部分将是确定分支上皮细胞所涉及组织的适当本构定律以及物理参数的量化。这只有通过理论指导的实验与实验指导的理论相结合才能有效地完成。在定量力学框架中设计和分析的机械数学建模、复杂模拟和实验的协同作用将 - 帮助支持或反驳假设的机制 - 阐明各种物理现象在创建管道分支系统中的相对作用 - 帮助推动生物医学的一部分走向未来，成为一门更精确的定量学科。

DESCRIPTION (provided by applicant): Objectives: The living world is embedded in the physical world. Small organisms live in a world of diffusion. The rest of us require a system of ducts for transport of all the materials we need to live. Systems of branched ducts are found in lung, kidney, mammary gland, and many other organs. This project's primary objective is to understand the mechanisms of tissue dynamics that create branched systems. It also aims to clarify the best ways to work with continuum mechanical models of morphogenesis to realistically describe mechanics and transport in developing tissues. Additionally, the project will develop new numerical methods for mixture models with interfaces. We will then test these models in a real time living branching system, the early embryonic lung. Aim 1: Develop accurate, stable, efficient methods for solving mixture problems with sharp interfaces. Aim 2: Develop a suite of models of the mechanical aspects of branching epithelia. Aim 3: Determine the morphogenetic effect of the mechanics internal to a branching epithelium. Aim 4: Determine the morphogenetic effect of the mechanics external to a branching epithelium. Part of this project will be a determination of the appropriate constitutive laws, as well as quantification of the physical parameters, of the tissues involved in branching epithelia. This can only be effectively done by theory-guided experiments in conjunction with experiment-guided theory. The synergy of mechanistic mathematical modeling, sophisticated simulation, and experiment designed and analyzed in a quantitative mechanical framework will - help support or refute hypothesized mechanisms - clarify the relative roles of various physical phenomena in creating branched systems of ducts - help drive a part of biomedicine towards the future as a more exactly quantitative discipline.