Epithelial Cell Migration: Model selectionn for mechanistic model development

University Of Colorado, Boulder CO

Investigators

Linked publications, trials & patents

Abstract

The collective migration of cells is a central biological process for multicellular organisms. While substantial research has been devoted to its study, we still lack a fundamental understanding of what drives groups of cells to move collectively in a single direction. The objective of this proposal is to advance our understanding of the causal mechanisms which induce the collective movement of cells through advanced mathematical modeling and novel experiments. This objective will be pursued in this context of studying the migration of keratinocytes during the epithelialization stage of wound healing. A central premise of this research is that advances in the study this phase of wound healing lead to a deeper understanding of the biochemical and mechanical signals that lie at the core of cellular migration. A central obstacle inhibiting deeper study of migration lies in the fact that there are large number of viable explanatory mechanisms. Toward this goal, we will use information-theoretic model selection criteria for dynamical systems to choose among several candidate models to find those which best represent the migration patterns - and thus those that best describe the underlying biology. This project builds on a close collaboration between the labs of an applied mathematician (Bortz), a cell biologist/biochemist (Liu), and a statistician (Dukie). It aims to transform scientific understanding of cellular migration by discovering previously unknown biochemical and physical mechanisms. The proposed investigation is a novel blend of advanced mathematical and statistical inquiry and experimental validation and reflects the ongoing synergistic efforts of the three labs.