TY - JOUR
T1 - Interplay of the physical microenvironment, contact guidance, and intracellular signaling in cell decision making
AU - Paul, Colin D.
AU - Shea, Daniel J.
AU - Mahoney, Megan R.
AU - Chai, Andreas
AU - Laney, Victoria
AU - Hung, Wei Chien
AU - Konstantopoulos, Konstantinos
N1 - Funding Information:
The authors thank Dr. Denis Wirtz (The Johns Hopkins University) for providing HT1080 cells. This study was supported by the U.S. National Institutes of Health, National Cancer Institute Grants R01-CA183804 and R01-CA186286 (to K.K.), and by a National Science Foundation Graduate Research Fellowship (to C.D.P.). The authors declare no conflicts of interest.
Publisher Copyright:
© FASEB.
PY - 2016/6
Y1 - 2016/6
N2 - The peritumoral physical microenvironment consists of complex topographies that influence cell migration. Cell decision making, upon encountering anisotropic, physiologically relevant physical cues, has yet to be elucidated. By integrating microfabrication with cell and molecular biology techniques, we provide a quantitative and mechanistic analysis of cell decision making in a variety of well-defined physical microenvironments. We used MDA-MB-231 breast carcinoma and HT1080 fibrosarcoma as cell models. Cell decision making after lateral confinement in 2-dimensional microcontact printed lines is governed by branch width at bifurcations. Cells confined in narrow feeder microchannels prefer to enter wider branches at bifurcations. In contrast, in feeder channels that are wider than the cell body, cells elongate along one side wall of the channel and are guided by contact with the wall to the contiguous branch channel independent of its width. Knockdown of β1-integrins or inhibition of cellular contractility suppresses contact guidance. Concurrent, but not individual, knockdown of nonmuscle myosin isoforms IIA and IIB also decreases contact guidance, which suggests the existence of a compensatory mechanism between myosin IIA and myosin IIB. Conversely, knockdown or inhibition of cell division control protein 42 homolog promotes contact guidance-mediated decision making. Taken together, the dimensionality, length scales of the physical microenvironment, and intrinsic cell signaling regulate cell decision making at intersections.
AB - The peritumoral physical microenvironment consists of complex topographies that influence cell migration. Cell decision making, upon encountering anisotropic, physiologically relevant physical cues, has yet to be elucidated. By integrating microfabrication with cell and molecular biology techniques, we provide a quantitative and mechanistic analysis of cell decision making in a variety of well-defined physical microenvironments. We used MDA-MB-231 breast carcinoma and HT1080 fibrosarcoma as cell models. Cell decision making after lateral confinement in 2-dimensional microcontact printed lines is governed by branch width at bifurcations. Cells confined in narrow feeder microchannels prefer to enter wider branches at bifurcations. In contrast, in feeder channels that are wider than the cell body, cells elongate along one side wall of the channel and are guided by contact with the wall to the contiguous branch channel independent of its width. Knockdown of β1-integrins or inhibition of cellular contractility suppresses contact guidance. Concurrent, but not individual, knockdown of nonmuscle myosin isoforms IIA and IIB also decreases contact guidance, which suggests the existence of a compensatory mechanism between myosin IIA and myosin IIB. Conversely, knockdown or inhibition of cell division control protein 42 homolog promotes contact guidance-mediated decision making. Taken together, the dimensionality, length scales of the physical microenvironment, and intrinsic cell signaling regulate cell decision making at intersections.
KW - Cell migration
KW - Confinement
KW - Microfluidics
UR - http://www.scopus.com/inward/record.url?scp=84971671191&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84971671191&partnerID=8YFLogxK
U2 - 10.1096/fj.201500199R
DO - 10.1096/fj.201500199R
M3 - Article
C2 - 26902610
AN - SCOPUS:84971671191
SN - 0892-6638
VL - 30
SP - 2161
EP - 2170
JO - FASEB Journal
JF - FASEB Journal
IS - 6
ER -