Microfluidic platform for the quantitative analysis of leukocyte migration signatures

Nat Commun. 2014 Sep 3;5:4787. doi: 10.1038/ncomms5787.

Abstract

Leukocyte migration into tissues is characteristic of inflammation. It is usually measured in vitro as the average displacement of populations of cells towards a chemokine gradient, not acknowledging other patterns of cell migration. Here, we designed and validated a microfluidic migration platform to simultaneously analyse four qualitative migration patterns: chemoattraction, -repulsion, -kinesis and -inhibition, using single-cell quantitative metrics of direction, speed, persistence and fraction of cells responding. We find that established chemokines, complement component 5a and IL-8 induce chemoattraction and repulsion in equal proportions, resulting in the dispersal of cells. These migration signatures are characterized by high persistence and speed and are independent of the chemokine dose or receptor expression. Furthermore, we find that twice as many T lymphocytes migrate away than towards stromal cell-derived factor 1 and their directional migration patterns are not persistent. Overall, our platform helps discover migratory signature responses and uncovers an avenue for precise characterization of leukocyte migration and therapeutic modulators.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chemokine CXCL12 / pharmacology
  • Chemotaxis / drug effects
  • Complement C5a / pharmacology*
  • Humans
  • Interleukin-8 / pharmacology*
  • Leukotriene B4 / pharmacology
  • Lymphocyte Count
  • Microfluidic Analytical Techniques
  • N-Formylmethionine Leucyl-Phenylalanine / pharmacology
  • Primary Cell Culture
  • T-Lymphocytes / cytology
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / immunology

Substances

  • CXCL12 protein, human
  • Chemokine CXCL12
  • Interleukin-8
  • Leukotriene B4
  • N-Formylmethionine Leucyl-Phenylalanine
  • Complement C5a