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

组织在我们的身体中执行着广泛的基本任务。它们负责器官的功能，允许举重，处理和传导电信号，并赋予身体和器官形状。后一项任务是由结缔组织完成的，其中包括软骨。在一个成年生物体中，主要的努力是维持现存组织的正常功能。然而，这些组织必须在胚胎发生期间首先发育，然后才能完成它们的最终目的。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。间充质与上皮细胞一起构成胚胎组织的主要细胞成分。此外，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，控制上皮细胞和间充质细胞之间转变以及两种细胞混合形成软骨的物理机制尚不清楚。此外，相关研究多集中在相关的化学信号上，往往忽略了组织力学特性的作用。最近的实验表明，细胞间的机械相互作用及其物理性质的变化对细胞间的转变和软骨的形成至关重要。因此，我想为这两种细胞类型的转变发展一个理论描述，并将其扩展到描述软骨是如何从上皮细胞和间充质细胞的混合物中形成的。为此，我想建立一个模拟模型和连续描述来预测组织的组成、力学性能和有序程度。所有的理论方法都应该经过相应的实验研究的检验。揭示物理原理，剖析参与可逆细胞类型转换和软骨形成的机械和生化过程的贡献，将有助于提高我们对胚胎发生过程中复杂组织发育的理解。这些知识可以有效地控制和指导组织工程中的细胞分化，为复杂人工组织的生长铺平道路。

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.