title: Engineered Models of Confined Cell Migration.
abstract: Cells in the body are physically confined by neighboring cells, tissues, and the extracellular matrix. Although physical confinement modulates intracellular signaling and the underlying mechanisms of cell migration, it is difficult to study in vivo. Furthermore, traditional two-dimensional cell migration assays do not recapitulate the complex topographies found in the body. Therefore, a number of experimental in vitro models that confine and impose forces on cells in well-defined microenvironments have been engineered. We describe the design and use of microfluidic microchannel devices, grooved substrates, micropatterned lines, vertical confinement devices, patterned hydrogels, and micropipette aspiration assays for studying cell responses to confinement. Use of these devices has enabled the delineation of changes in cytoskeletal reorganization, cell-substrate adhesions, intracellular signaling, nuclear shape, and gene expression that result from physical confinement. These assays and the physiologically relevant signaling pathways that have been elucidated are beginning to have a translational and clinical impact.
authors.affiliation: Department of Chemical and Biomolecular Engineering.|Institute for NanoBioTechnology, and.
authors.forename: Colin D
authors.initials: CD
authors.lastname: Paul
authors.affiliation: Department of Chemical and Biomolecular Engineering.|Institute for NanoBioTechnology, and.
authors.forename: Wei-Chien
authors.initials: WC
authors.lastname: Hung
authors.affiliation: Department of Chemical and Biomolecular Engineering.|Institute for NanoBioTechnology, and.|Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland 21218; email: konstant@jhu.edu.
authors.forename: Denis
authors.initials: D
authors.lastname: Wirtz
authors.affiliation: Department of Chemical and Biomolecular Engineering.|Institute for NanoBioTechnology, and.|Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland 21218; email: konstant@jhu.edu.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Konstantopoulos
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured / Q000502:physiology*; D003599:Cytoskeleton / Q000502:physiology*; D006801:Humans; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D044085:Microfluidics / Q000379:methods*; D008846:Micromanipulation / Q000379:methods*
keywords: cell confinement; cell migration; cytoskeletal organization; mechanosensing; microfluidics; micropatterning