Modeling and Computational Studies of Cell and Tissue Movement

9805494，首席研究员和他的同事建立并分析了非相互作用的单个细胞的运动和细胞强烈相互作用的细胞聚集体的运动的数学模型。他们使用细胞黏液霉菌盘基网柄菌作为模型系统，因为它既体现了单个细胞的自由运动，也体现了集合体的集体运动，也因为它被广泛用作研究细胞运动的模型实验系统。在这个系统上有大量的实验数据，几个实验室已经同意在新数据可用时共享这些数据。同时进行三个相辅相成的次级项目。第一个是研究基于单个细胞的模型，该模型结合了内部结构和主动作用力的产生，并允许研究人员评估关于单个细胞运动的各种理论建议。第二种是建立一个更高层次的基于细胞的模型，用于分析许多细胞的集体运动；第三种是采用连续介质方法，将细胞系统建模为粘弹性流体，细胞内的应力和细胞之间的粘弹性相互作用对应力张量有贡献。目前有关运动的信息被用于模型的制定，与实验小组的持续互动提供了关于模型有效性的反馈，并使研究人员能够建议实验来测试模型。然而，关于细胞和组织运动的知识不仅适用于盘基网柄菌，而且还可以用于其他几种情况，包括胚胎发育、伤口愈合和免疫系统。细胞和组织的运动在许多生物体的整个生命周期中起着至关重要的作用。细菌和其他单细胞生物通过向有利的方向游动来寻找食物和躲避驱虫物，人类免疫系统中的巨噬细胞等细胞必须检测感染部位并向它们移动，才能摄取细菌和细胞碎片。在组织水平上，细胞聚集体的协调运动在早期胚胎发育和伤口愈合等不同过程中发挥着关键作用。因此，重要的是要更好地了解细胞运动及其控制，无论是在细胞单独运动的低密度区域，还是在细胞强烈相互作用和集体运动的组织密度区域。数学建模可以通过测试目前技术难以在实验中检验的假设，在理解这些过程中发挥重要作用。例如，更好地了解细胞和组织如何运动将有助于更好地理解细菌生物膜的形成和控制，细菌生物膜在医疗移植等环境中是有害的，但在污染控制和药物生产等环境中是有价值的。

Othmer 9805494 The principal investigator and his colleagues formulate and analyze mathematical models for the motion of individual, non-interacting cells and for the collective motion of cellular aggregates in which cells interact strongly. They use the cellular slime mold Dictyostelium discoideum as the model system because it exemplifies both the free-ranging movement of individual cells and the collective motion of aggregates, and because it is widely used as a model experimental system for the study of cell movement. There is a large body of experimental data on this system, and several labs have agreed to share their new data as it becomes available. Three complementary subprojects are pursued in parallel. The first is to investigate an individual cell-based model that incorporates internal structure and active force generation and allows the investigators to evaluate various theoretical proposals for individual cell movement. The second involves the formulation of a higher-level, cell-based model used for analyzing the collective motion of many cells, and the third employs a continuum approach in which the cellular system is modeled as a viscoelastic fluid with contributions to the stress tensor from both the intracellular stress and the viscoelastic interactions between cells. Current information on the movement is used in the formulation of the models, and the ongoing interaction with experimental groups provides feedback on the validity of the models and enables the investigators to suggest experiments to test the models. However, what is learned on cell and tissue movement not only is applicable to Dictyostelium discoideum, but also can be used in several other contexts, including embryonic development, wound healing, and the immune system. Cell and tissue movement plays a vital role throughout the lifespan of many organisms. Bacteria and other single-cell organisms find food and avoid repellents by swimming in favorable directions, and cells such as macrophages in the human immune system must detect sites of infection and move toward them in order to ingest bacteria and cellular debris. At the tissue level, the coordinated movement of aggregates of cells plays a critical part in such diverse processes as early embryonic development and wound healing. Thus it is important to develop a better understanding of cell movement and its control, both in the low-density regime where cells move individually, and at tissue-level densities where cells interact strongly and move collectively. Mathematical modeling can play an important role in understanding these processes by testing hypotheses that are difficult to test experimentally with current technology. A better understanding of how cells and tissues move will lead, for example, to a better understanding of the formation and control of bacterial biofilms, which are deleterious in contexts such as medical transplants, but valuable in contexts such as pollution control and drug production.