This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5).
Cell crawling is integral to many important biological and biomedical processes, such as wound healing, cancer metastasis, and organism development. A quantitatively predictive model that describes the bulk motion of many cells will have broad impact across many areas of biology and biophysics. This research will combine the general physical features of single cell crawling with a physiologically realistic description of cell-cell adhesion and cell-cell interaction in order to develop a mathematical model for the collective movements of cells in tissue. Specifically, the model will address a number of experimentally-measured behaviors that occur in wound healing assays. For example, recent experiments have shown that there are complex motions and long-range correlations of the movements of cells in epithelial monolayers. In addition, during wound healing assays it is observed that the wound edge undergoes a fingering-like instability, and the average progression of the wound border expands at a supra-linear rate with respect to time. This research will develop and test a continuum model for the collective migration of eukaryotic cells in tissue, with an emphasis toward explaining the dynamics of epithelial cell monolayers during wound closure. Most of the model parameters will be set using existing experimental data; however, some parameters are currently unknown. Therefore, comparison of the model with existing experimental data will allow us to set ranges on these unknown parameters and will suggest new experiments to test the predictions of the model. Analytic and numerical methods will be used to analyze the model for free boundary problems corresponding to two different wound closure experiments, and the model will be used to explore three-dimensional motility in bulk tissue.
To build an organism out of a vast number of cells requires coordination and the ability to move cells from one place to another. Therefore, during development of an organism, it is not surprising that groups of cells often migrate together, as a semi-cohesive unit. Similar migratory behavior is also seen during wound healing and cancer metastasis. This project explores the physics of this motility and the mechanism by which the physical behavior of cells helps maintain the overall coordination of the group. A mathematical model will be developed that takes into account the gross behavior of motile cells, considering the forces generated by an individual cell and the interactions between neighboring cells. This model will be used to describe the behavior of a wounded layer of cells, and the predictions will be tested by comparing them to data from experiments that mimic wounded tissues. The results from this project will provide a deeper understanding of many important biological processes, such as organism development, cancer metastasis, and even the motions of dense communities of swimming bacteria. The strong interdisciplinary nature of the research makes it ideal for training graduate students and postdoctoral researchers to be able to work at the interface between biology, mathematics, and physics.
