title: Study of Chemotaxis and Cell-Cell Interactions in Cancer with Microfluidic Devices.
abstract: Microfluidic devices have very broad applications in biological assays from simple chemotaxis assays to much more complicated 3D bioreactors. In this chapter, we describe the design and methods for performing chemotaxis assays using simple microfluidic chemotaxis chambers. With these devices, using real-time video microscopy we can examine the chemotactic responses of neutrophil-like cells under conditions of varying gradient steepness or flow rate and then utilize software programs to calculate the speed and angles of cell migration as gradient steepness and flow are varied. Considering the shearing force generated on the cells by the constant flow that is required to produce and maintain a stable gradient, the trajectories of the cell migration will reflect the net result of both shear force generated by flow and the chemotactic force resulting from the chemokine gradient. Moreover, the effects of mutations in chemokine receptors or the presence of inhibitors of intracellular signals required for gradient sensing can be evaluated in real time. We also describe a method to monitor intracellular signals required for cells to alter cell polarity in response to an abrupt switch in gradient direction. Lastly, we demonstrate an in vitro method for studying the interactions of human cancer cells with human endothelial cells, fibroblasts, and leukocytes, as well as environmental chemokines and cytokines, using 3D microbioreactors that mimic the in vivo microenvironment.
authors.affiliation: Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, Tennessee, USA; Department of Cancer Biology, School of Medicine, Vanderbilt University, Nashville, Tennessee, USA.
authors.forename: Jiqing
authors.initials: J
authors.lastname: Sai
authors.affiliation: Vanderbilt Institute for Integrative Biosystems Research and Education, Vanderbilt University, Nashville, Tennessee, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Rogers
authors.affiliation: Vanderbilt Institute for Integrative Biosystems Research and Education, Vanderbilt University, Nashville, Tennessee, USA.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Hockemeyer
authors.affiliation: Vanderbilt Institute for Integrative Biosystems Research and Education, Vanderbilt University, Nashville, Tennessee, USA; Department of Biomedical Engineering, Vanderbilt University, Nashville, Tennessee, USA; Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee, USA; Department of Physics and Astronomy, Vanderbilt University, Nashville, Tennessee, USA.
authors.forename: John P
authors.initials: JP
authors.lastname: Wikswo
authors.affiliation: Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, Tennessee, USA; Department of Cancer Biology, School of Medicine, Vanderbilt University, Nashville, Tennessee, USA; Vanderbilt Institute for Integrative Biosystems Research and Education, Vanderbilt University, Nashville, Tennessee, USA. Electronic address: ann.richmond@vanderbilt.edu.
authors.forename: Ann
authors.initials: A
authors.lastname: Richmond
mesh_terms: D000818:Animals; D002450:Cell Communication; D002465:Cell Movement; D002478:Cells, Cultured; D018925:Chemokines / Q000378:metabolism; D002633:Chemotaxis; D004867:Equipment Design; D018922:HL-60 Cells; D006801:Humans; D056656:Lab-On-A-Chip Devices; D046210:Microfluidic Analytical Techniques; D044085:Microfluidics / Q000295:instrumentation* / Q000379:methods*; D009369:Neoplasms / Q000473:pathology*; D059016:Tumor Microenvironment
chemical_list: D018925:Chemokines
keywords: CXCR2; Chemotaxis; Gradient switch; Microbioreactor; Microfluidic device; Polarization; Tumor microenvironment