Modeling and Computational Studies of Cell and Tissue Movement

细胞和组织运动的建模和计算研究

• 批准号: 9805494
• 负责人: Hans Othmer
• 金额: $ 42万
• 依托单位: University of Utah
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-15 至 2000-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9805494&HistoricalAwards=false
• 关键词: Modeling; Computational; Studies; Cell; Tissue

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.

Othmer 9805494 首席研究员和他的同事制定并分析了个体、非相互作用细胞运动以及细胞强烈相互作用的细胞聚集体集体运动的数学模型。 他们使用细胞黏菌Dictyosteelium discoideum作为模型系统，因为它证实了单个细胞的自由运动和聚集体的集体运动，并且因为它被广泛用作研究细胞运动的模型实验系统。 这个系统有大量的实验数据，几个实验室已经同意分享他们的新数据，因为它变得可用。 三个相辅相成的次级项目同时进行。 第一个是研究一个基于单个细胞的模型，该模型结合了内部结构和主动力的产生，并允许研究人员评估单个细胞运动的各种理论建议。 第二个涉及制定一个更高层次的，基于细胞的模型用于分析许多细胞的集体运动，和第三个采用连续的方法，其中细胞系统被建模为粘弹性流体的贡献，从细胞内的应力和细胞之间的粘弹性相互作用的应力张量。 当前的运动信息用于模型的制定，与实验组的持续互动提供了对模型有效性的反馈，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研究不仅适用于盘基网柄藻，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并避免驱虫剂，而人类免疫系统中的细胞（如巨噬细胞）必须检测感染部位并向它们移动，以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起着关键作用。 因此，重要的是要更好地了解细胞运动及其控制，无论是在低密度制度，细胞单独移动，并在组织水平的密度，细胞强烈相互作用，集体移动。 数学建模可以在理解这些过程中发挥重要作用，通过测试现有技术难以通过实验测试的假设。 例如，更好地了解细胞和组织如何移动将有助于更好地了解细菌生物膜的形成和控制，细菌生物膜在医疗移植等背景下是有害的，但在污染控制和药物生产等背景下是有价值的。