Autocrine signal transmission with extracellular ligand degradation

Document Type

Article

Publication Date

1-1-2009

Abstract

Traveling waves of cell signaling in epithelial layers orchestrate a number of important processes in developing and adult tissues. These waves can be mediated by positive feedback autocrine loops, a mode of cell signaling where binding of a diffusible extracellular ligand to a cell surface receptor can lead to further ligand release. We formulate and analyze a biophysical model that accounts for ligand-induced ligand release, extracellular ligand diffusion and ligand-receptor interaction. We focus on the case when the main mode for ligand degradation is extracellular and analyze the problem with the sharp threshold positive feedback nonlinearity. We derive expressions that link the speed of propagation and other characteristics of traveling waves to the parameters of the biophysical processes, such as diffusion rates, receptor expression level, etc. Analyzing the derived expressions we found that traveling waves in such systems can exhibit a number of unusual properties, e.g. non-monotonic dependence of the speed of propagation on ligand diffusivity. Our results for the fully developed traveling fronts can be used to analyze wave initiation from localized perturbations, a scenario that frequently arises in the in vitro models of epithelial wound healing, and guide future modeling studies of cell communication in epithelial layers. © 2009 IOP Publishing Ltd.

Identifier

64149099127 (Scopus)

Publication Title

Physical Biology

External Full Text Location

https://doi.org/10.1088/1478-3975/6/1/016006

e-ISSN

14783975

ISSN

14783967

PubMed ID

19234361

Issue

1

Volume

6

Grant

R01GM076690

Fund Ref

National Institute of General Medical Sciences

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