Modeling and Computational Studies of Cell and Tissue Movement

点击翻译按钮获取中文摘要

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.