Format

Send to

Choose Destination
See comment in PubMed Commons below
Integr Biol (Camb). 2013 Mar;5(3):481-94. doi: 10.1039/c3ib20249f.

Convolution of chemoattractant secretion rate, source density, and receptor desensitization direct diverse migration patterns in leukocytes.

Author information

1
Dept. of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

Abstract

Chemoattractants regulate diverse immunological, developmental, and pathological processes, but how cell migration patterns are shaped by attractant production in tissues remains incompletely understood. Using computational modeling and chemokine-releasing microspheres (CRMs), cell-sized attractant-releasing beads, we analyzed leukocyte migration in physiologic gradients of CCL21 or CCL19 produced by beads embedded in 3D collagen gels. Individual T-cells that migrated into contact with CRMs exhibited characteristic highly directional migration to attractant sources independent of their starting position in the gradient (and thus independent of initial gradient strength experienced) but the fraction of responding cells was highly sensitive to position in the gradient. These responses were consistent with modeling calculations assuming a threshold absolute difference in receptor occupancy across individual cells of ~10 receptors required to stimulate chemotaxis. In sustained gradients eliciting low receptor desensitization, attracted T-cells or dendritic cells swarmed around isolated CRMs for hours. With increasing CRM density, overlapping gradients and high attractant concentrations caused a transition from local swarming to transient "hopping" of cells bead to bead. Thus, diverse migration responses observed in vivo may be determined by chemoattractant source density and secretion rate, which govern receptor occupancy patterns in nearby cells.

PMID:
23392181
PMCID:
PMC3597436
DOI:
10.1039/c3ib20249f
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Royal Society of Chemistry Icon for PubMed Central
    Loading ...
    Support Center