title: Microfluidic platform for the quantitative analysis of leukocyte migration signatures.
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.
authors.affiliation: Transplant Research Program and The Division of Nephrology, Department of Medicine, Boston Children's Hospital, Boston, MA 02115, and the Department of Pediatrics, Harvard Medical School, Boston, MA 02115.|BioMEMS Resource Center, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Shriners Hospitals for Children, Boston, MA 02129.
authors.forename: Leo
authors.initials: L
authors.lastname: Boneschansker
authors.affiliation: BioMEMS Resource Center, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Shriners Hospitals for Children, Boston, MA 02129.
authors.forename: Jun
authors.initials: J
authors.lastname: Yan
authors.affiliation: BioMEMS Resource Center, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Shriners Hospitals for Children, Boston, MA 02129.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Wong
authors.affiliation: Transplant Research Program and The Division of Nephrology, Department of Medicine, Boston Children's Hospital, Boston, MA 02115, and the Department of Pediatrics, Harvard Medical School, Boston, MA 02115.
authors.forename: David M
authors.initials: DM
authors.lastname: Briscoe
authors.affiliation: BioMEMS Resource Center, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Shriners Hospitals for Children, Boston, MA 02129.
authors.forename: Daniel
authors.initials: D
authors.lastname: Irimia
mesh_terms: D054377:Chemokine CXCL12 / Q000494:pharmacology; D002633:Chemotaxis / Q000187:drug effects; D015936:Complement C5a / Q000494:pharmacology*; D006801:Humans; D016209:Interleukin-8 / Q000494:pharmacology*; D007975:Leukotriene B4 / Q000494:pharmacology; D018655:Lymphocyte Count; D046210:Microfluidic Analytical Techniques; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D061251:Primary Cell Culture; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology
chemical_list: C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D016209:Interleukin-8; D007975:Leukotriene B4; D009240:N-Formylmethionine Leucyl-Phenylalanine; D015936:Complement C5a