title: Automated co-culture system for spatiotemporal analysis of cell-to-cell communication.
abstract: We present a microfluidic co-culture system that generates localized and precisely formulated immune signals among a population of cells, enabling spatiotemporal analysis of paracrine signal transmission between different cell types. The automated system allows us to create temporally modulated chemical inputs that can be delivered to single signal-transmitting and receiving cells in a highly controlled way. Using this system we stimulated a single macrophage with brief pulses of bacterial LPS and observed the macrophage transmitted TNF signal propagating in a population of fibroblasts via NF-κB activation. The signal receiving fibroblasts transformed the TNF signal into a spatiotemporally distributed NF-κB output, recapitulating the initiation of immune response to bacterial infection.
authors.affiliation: Department of Biosystems Science and Engineering, ETH Zürich, Mattenstrasse 26, 4058 Basel, Switzerland. savas.tay@bsse.ethz.ch.
authors.forename: Tino
authors.initials: T
authors.lastname: Frank
authors.forename: Savaş
authors.initials: S
authors.lastname: Tay
mesh_terms: D000818:Animals; D001331:Automation; D018929:Cell Culture Techniques / Q000295:instrumentation* / Q000379:methods*; D018920:Coculture Techniques / Q000295:instrumentation / Q000379:methods; D005347:Fibroblasts / Q000166:cytology / Q000276:immunology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D018345:Mice, Knockout; D016328:NF-kappa B / Q000276:immunology*; D041681:NIH 3T3 Cells; D019899:Paracrine Communication / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D008070:Lipopolysaccharides; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha