TY - JOUR
T1 - Engineered Models of Confined Cell Migration
AU - Paul, Colin D.
AU - Hung, Wei Chien
AU - Wirtz, Denis
AU - Konstantopoulos, Konstantinos
N1 - Publisher Copyright:
© Copyright 2016 by Annual Reviews. All rights reserved.
PY - 2016/7/11
Y1 - 2016/7/11
N2 - 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.
AB - 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.
KW - Cell confinement
KW - Cell migration
KW - Cytoskeletal organization
KW - Mechanosensing
KW - Microfluidics
KW - Micropatterning
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U2 - 10.1146/annurev-bioeng-071114-040654
DO - 10.1146/annurev-bioeng-071114-040654
M3 - Review article
C2 - 27420571
AN - SCOPUS:84979031802
SN - 1523-9829
VL - 18
SP - 159
EP - 180
JO - Annual Review of Biomedical Engineering
JF - Annual Review of Biomedical Engineering
ER -