From the Physics of the Epithelial-Mesenchymal Transition to Cartilage Formation

组织在我们的身体中执行广泛的基本任务。它们负责器官的功能，允许举重，处理和传导电信号，并塑造身体和器官。后一项任务由结缔组织类完成，其中包括软骨作为一个例子。在成年生物体中，主要的奋进是保持现有组织的适当功能。然而，这些组织必须首先在胚胎发生期间发育，然后才能实现其最终目的。在胚胎中有一种特殊的细胞表型，即间充质细胞，它参与了几乎所有的发育过程。间充质细胞与上皮细胞一起构成胚胎组织的主要细胞成分，并且它们可以可逆地转化为上皮细胞并分化为其他细胞表型，如软骨细胞。后者与细胞外物质一起构成软骨。到目前为止，其物理机制尚不清楚，其控制上皮细胞和间充质细胞之间的转化以及由两种细胞类型的混合物形成软骨。此外，相关的研究大多集中在所涉及的化学信号上，而往往忽略了组织的力学性质的作用。最近的实验表明，细胞之间的力学相互作用并且它们的物理性质的变化对于细胞-细胞转变和在软骨形成期间至关重要。因此，我想发展一个理论描述的两种细胞类型的过渡，并扩展它来描述软骨是如何形成的上皮细胞和间充质细胞的混合物。为此，我想构建一个模拟模型和一个连续的描述来预测组织的组成，机械性能和有序度。 所有的理论方法都应该通过相应的实验研究来检验，揭示物理原理，剖析机械和生物化学过程的贡献，这些过程涉及可逆的细胞类型转换和软骨的形成，将有助于提高我们对胚胎发育过程中复杂组织发育的理解，这些知识将有助于有效地控制和指导组织中的细胞分化这可能为培养复杂的人造组织铺平道路。

Tissues perform a broad range of essential tasks in our body.They are responsible for the functionality of organs, allow to lift weights, process and conduct electric signals, and give shape to the body and the organs.The later task is accomplished by the class of connective tissues, which includescartilage as an example. In an adult organism, a major endeavor is to maintain the proper functionality of the exiting tissues. However, these tissues have to develop first during embryogenesis before they can fulfill their final purpose. In an embryo there is a special cell phenotype, the mesenchymal cell, which is involved in mostly all developmental processes. Together with epithelial cells, mesenchymes constitute the major cellular component in embryonic tissues.Moreover, they can reversibly transform to epithelial cells and differentiate to other cell phenotypes such as chondrocytes. The later, together with the extracellular material, makes up cartilage.So far the physical mechanisms are unknown, which govern the transition between epithelial and mesenchymal cells and the formation of cartilage from a mixture of both cell types.Additionally, related research mostly focuses on the involved chemical signals and often neglects the role of mechanical properties of the tissue.Recent experiments indicate that mechanical interactions between cells and changes of their physical properties are crucial for the cell-cell transitions and during the formation of cartilage. Thus I would like to develop a theoretical description for the transition of both cell types and extend it to describe how cartilage forms from of a mixture of epithelial and mesenchymal cells. To this end I would like to construct a simulation model and a continuous description to predict the composition, the mechanical properties and the degree of order of the tissue. All theoretical approaches should be scrutinized by corresponding experimental studies.Unravelling the physical principles, and dissecting the contributions of mechanical andbiochemical processes, which are involved in the reversible cell type transitions and the formation of cartilage, will help to improve our understanding on the development of complex tissues during embryogenesis.This knowledge could allow to efficiently control and guide cell Differentiation in tissue engineering which might pave the way to grow complex artificial tissues.