Mathematical Modeling and Computational Analysis of Cell and Tissue Movement

University Of Minnesota-Twin Cities, Minneapolis MN

Investigators

Abstract

Othmer and Stolarska The investigators formulate and analyze mathematical models for signal transduction, direction sensing, and movement in individual, non-interacting amoeboid cells and incorporate the individual-based model in models for the collective motion of tissue-like cellular aggregates in which the cells interact strongly. The cellular slime mold Dictyostelium discoideum is used 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. Current information on movement of Dictyostelium is used in the formulation of the mathematical models, and interaction with different experimental groups provides feedback on the validity of the models. Suitable computational techniques to simulate the resulting partial differential equations are developed. What is learned about cell and tissue movement is applicable to Dictyostelium; it can be used in several other contexts, including embryonic development, wound healing, angiogenesis, and the immune system. Macroscopic descriptions based on microscopic models of cell behavior will significantly improve large-scale tissue simulations and expand the scope of feasible, microscopically-accurate simulations. In this project the investigators develop mathematical models to help understand how signal transduction, direction sensing, and movement in individual, non-interacting cells of Dictyostelium discoideum, a cellular slime mold, contribute to the collective behavior of large aggregates of cells. Directed cell migration plays an essential role in the early development and ongoing maintenance of most organisms. Single-cell organisms such as bacteria find food and avoid repellents by chemotaxis, leukocytes must detect sites of infection and move toward them in order to ingest bacteria and cellular debris, and directed cell migration is essential for embryonic development and wound healing. Cell migration also occurs in many diseases; in cancer, for instance, it leads to invasion and metastasis, and cell adhesion and motility also have important roles there. Metastasis is probably the major cause of death in cancer patients. The potential impact of a better understanding of cell motion is enormous. Not only is control of motility an important therapeutic target for cancer treatment, but cell and tissue engineering holds the promise to provide new tissues and organs by in vivo tissue regeneration. The success of this hinges on understanding the ways that cells attach to natural and artificial extracellular matrix, as well as the characteristics of the cell-cell interactions that eventually dictate how cells move, proliferate and remodel into new capillaries or other types of functional tissues.