Convolution of chemoattractant secretion rate, source density, and receptor desensitization direct diverse migration patterns in leukocytes
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Author(s)
Wang, Yana
Irvine, Darrell J
Date Issued
2013
Journal
Integrative Biology
Publisher
Royal Society of Chemistry
Citation
Wang, Yana, and Darrell J. Irvine. “Convolution of Chemoattractant Secretion Rate, Source Density, and Receptor Desensitization Direct Diverse Migration Patterns in Leukocytes.” Integr. Biol. 5, no. 3 (2013): 481.
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Author's final manuscript
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 CCL21or 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 [similar]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.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Chemical Engineering
Massachusetts Institute of Technology. Department of Materials Science and Engineering
Ragon Institute of MGH, MIT and Harvard
Koch Institute for Integrative Cancer Research at MIT
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DOI of Published Version
https://doi.org/10.1039/c3ib20249f
