An integrated stochastic model of "inside-out" integrin activation and selective T-lymphocyte recruitment Academic Article uri icon

Overview

MeSH Major

  • Integrins
  • Models, Biological
  • T-Lymphocytes

abstract

  • The pattern of T-lymphocyte homing is hypothesized to be controlled by combinations of chemokine receptors and complementary chemokines. Here, we use numerical simulation to explore the relationship among chemokine potency and concentration, signal transduction, and adhesion. We have developed a form of adhesive dynamics-a mechanically accurate stochastic simulation of adhesion-that incorporates stochastic signal transduction using the next subvolume method. We show that using measurable parameter estimates derived from a variety of sources, including signaling measurements that allow us to test parameter values, we can readily simulate approximate time scales for T-lymphocyte arrest. We find that adhesion correlates with total chemokine receptor occupancy, not the frequency of occupation, when multiple chemokine receptors feed through a single G-protein. A general strategy for selective T-lymphocyte recruitment appears to require low affinity chemokine receptors. For a single chemokine receptor, increases in multiple cross-reactive chemokines can lead to an overwhelming increase in adhesion. Overall, the methods presented here provide a predictive framework for understanding chemokine control of T-lymphocyte recruitment.

publication date

  • January 31, 2012

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3269544

Digital Object Identifier (DOI)

  • 10.1021/la203803e

PubMed ID

  • 22149624

Additional Document Info

start page

  • 2225

end page

  • 37

volume

  • 28

number

  • 4