TY - JOUR
T1 - Dorsoventral polarity directs cell responses to migration track geometries
AU - Wisniewski, Emily O.
AU - Mistriotis, Panagiotis
AU - Bera, Kaustav
AU - Law, Robert A.
AU - Zhang, Jitao
AU - Nikolic, Milos
AU - Weiger, Michael
AU - Parlani, Maria
AU - Tuntithavornwat, Soontorn
AU - Afthinos, Alexandros
AU - Zhao, Runchen
AU - Wirtz, Denis
AU - Kalab, Petr
AU - Scarcelli, Giuliano
AU - Friedl, Peter
AU - Konstantopoulos, Konstantinos
N1 - Publisher Copyright:
© 2020 The Authors.
PY - 2020/7
Y1 - 2020/7
N2 - How migrating cells differentially adapt and respond to extracellular track geometries remains unknown. Using intravital imaging, we demonstrate that invading cells exhibit dorsoventral (top-to-bottom) polarity in vivo. To investigate the impact of dorsoventral polarity on cell locomotion through different confining geometries, we fabricated microchannels of fixed cross-sectional area, albeit with distinct aspect ratios. Vertical confinement, exerted along the dorsoventral polarity axis, induces myosin II-dependent nuclear stiffening, which results in RhoA hyperactivation at the cell poles and slow bleb-based migration. In lateral confinement, directed perpendicularly to the dorsoventral polarity axis, the absence of perinuclear myosin II fails to increase nuclear stiffness. Hence, cells maintain basal RhoA activity and display faster mesenchymal migration. In summary, by integrating microfabrication, imaging techniques, and intravital microscopy, we demonstrate that dorsoventral polarity, observed in vivo and in vitro, directs cell responses in confinement by spatially tuning RhoA activity, which controls bleb-based versus mesenchymal migration.
AB - How migrating cells differentially adapt and respond to extracellular track geometries remains unknown. Using intravital imaging, we demonstrate that invading cells exhibit dorsoventral (top-to-bottom) polarity in vivo. To investigate the impact of dorsoventral polarity on cell locomotion through different confining geometries, we fabricated microchannels of fixed cross-sectional area, albeit with distinct aspect ratios. Vertical confinement, exerted along the dorsoventral polarity axis, induces myosin II-dependent nuclear stiffening, which results in RhoA hyperactivation at the cell poles and slow bleb-based migration. In lateral confinement, directed perpendicularly to the dorsoventral polarity axis, the absence of perinuclear myosin II fails to increase nuclear stiffness. Hence, cells maintain basal RhoA activity and display faster mesenchymal migration. In summary, by integrating microfabrication, imaging techniques, and intravital microscopy, we demonstrate that dorsoventral polarity, observed in vivo and in vitro, directs cell responses in confinement by spatially tuning RhoA activity, which controls bleb-based versus mesenchymal migration.
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U2 - 10.1126/sciadv.aba6505
DO - 10.1126/sciadv.aba6505
M3 - Article
C2 - 32789173
AN - SCOPUS:85089609938
SN - 2375-2548
VL - 6
JO - Science Advances
JF - Science Advances
IS - 31
M1 - aba6505
ER -