title: Neutrophil migration under spatially-varying chemoattractant gradient profiles.
abstract: Chemotaxis plays an important role in biological processes such as cancer metastasis, embryogenesis, wound healing, and immune response. Neutrophils are the frontline defenders against invasion of foreign microorganisms into our bodies. To achieve this important immune function, a neutrophil can sense minute chemoattractant concentration differences across its cell body and effectively migrate toward the chemoattractant source. Furthermore, it has been demonstrated in various studies that neutrophils are highly sensitive to changes in the surrounding chemoattractant environments, suggesting the role of a chemotactic memory for processing the complex spatiotemporal chemical guiding signals. Using a microfluidic device, in the present study we characterized neutrophil migration under spatially varying profiles of interleukine-8 gradients, which consist of three spatially ordered regions of a shallow gradient, a steep gradient and a nearly saturated gradient. This design allowed us to examine how neutrophils migrate under different chemoattractant gradient profiles, and how the migratory response is affected when the cell moves from one gradient profile to another in a single experiment. Our results show robust neutrophil chemotaxis in the shallow and steep gradient, but not the saturated gradient. Furthermore, neutrophils display a transition from chemotaxis to flowtaxis when they migrate across the steep gradient interface, and the relative efficiency of this transition depends on the cell's chemotaxis history. Finally, some neutrophils were observed to adjust their morphology to different gradient profiles.
authors.affiliation: Department of Physics and Astronomy, University of Manitoba, Winnipeg, MB, R3T 2N2, Canada.
authors.forename: Iris
authors.initials: I
authors.lastname: Halilovic
authors.forename: Jiandong
authors.initials: J
authors.lastname: Wu
authors.forename: Murray
authors.initials: M
authors.lastname: Alexander
authors.forename: Francis
authors.initials: F
authors.lastname: Lin
mesh_terms: D001783:Blood Flow Velocity / Q000502:physiology; D002478:Cells, Cultured; D002630:Chemotactic Factors / Q000008:administration & dosage; D002633:Chemotaxis / Q000187:drug effects / Q000502:physiology*; D004867:Equipment Design; D019544:Equipment Failure Analysis; D006801:Humans; D016209:Interleukin-8 / Q000008:administration & dosage*; D056656:Lab-On-A-Chip Devices; D018375:Neutrophil Activation / Q000187:drug effects* / Q000502:physiology*; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D062211:Spatio-Temporal Analysis
chemical_list: D002630:Chemotactic Factors; D016209:Interleukin-8