The power of systems biology lies in its potential to explain complex macroscale phenomenon in terms of molecular properties and activities. Arriving at such an ultimate understanding requires layered models and quantitative experiments that span every length scale. Our laboratory is interested in the phenomenon of sheet migration - a key process in wound healing and animal development. Here I will emphasize two projects that have helped us define the boundaries of this problem. First, I will describe an agent based model of that predicts the most robust features of sheet migration seen in scratch wound assays in our lab and throughout the literature. In this model we imbue cellular agents with the motility and division dynamics we measure for individual cells. Significantly, our model predicts that biochemical cell-cell communication is not required for the migration of cells as a collective in the scratch wound. Instead we show that ability of cells to sense and respond to contact with redirected migration allows cellular agents to quantitatively reproduce experimental healing rates and patterns. Second, I will describe our continuing effort to build a comprehensive model of the actin cycle - the engine that drives cell migration in nearly every eukaryotic cell. In this model we represent actin and its key regulatory proteins to predict system level quantities such as flux, turnover, and degree of polymerization. Significantly, our observations at the cellular level hint that the arrest of actin dynamics at the leading edge of a migrating cell might explain the sensitivity of cells to collisions. Thus connecting our cellular and molecular models to explain sheet migration will require an intermediate model that predicts how cell-cell contacts impact actin dynamics.
Copyright. All Rights Reserved.