Quantitative Analysis of Cell Signaling Dynamics During Cell Migration and Cell Fate Decisions

Quantitative Analysis of Cell Signaling Dynamics During Cell Migration and Cell Fate Decisions

Xuedong Liu, Ph.D. Department of Chemistry and Biochemistry University of Colorado-Boulder Boulder, CO 80303 Email: liux@colorado.edu

Abstract

Cells adapt to their environments largely through the activities of signal transduction networks. Understanding cell signaling complexity will require adopting a system view of cell function in which the discovery of new molecules and connections is combined with studies of system dynamics. One of the cell signaling systems we studies is TGF-β, a prominent signaling pathways crucial for regulating diverse aspects of cellular homeostasis. We have been studying how cells read TGF-β concentration with high precision to produce different biological responses using a combined experimental and modeling approach. We demonstrated that TGF-β ligand dynamics can be the principal determinant of the Smad signal duration and account for long term ultrasensitive response to TGF-β signaling. The significance of cellular context in governing the outcomes of TGF-β signaling is investigated during collective epithelial sheet migration. Here TGF-ß modulates MAPK signaling networks in spatiotemporal manner to control the mode of cell migration. Finally, I will discuss an example of an adaptive cell signaling system where the tandem action of two different enzymes mediates mutually exclusive cell fate decisions in response to different cell stress stimuli.