Dorsoventral polarity directs cell responses to migration track geometries.

Journal

Science advances
ISSN: 2375-2548
Titre abrégé: Sci Adv
Pays: United States
ID NLM: 101653440

Informations de publication

Date de publication:
07 2020
Historique:
received: 20 12 2019
accepted: 12 06 2020
entrez: 14 8 2020
pubmed: 14 8 2020
medline: 14 8 2020
Statut: epublish

Résumé

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.

Identifiants

DOI: 10.1126/sciadv.aba6505 PMID: 32789173 PMC: PMC7399493
pubmed: 32789173
doi: 10.1126/sciadv.aba6505
pii: aba6505
pmc: PMC7399493
doi:

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S. Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

eaba6505

Subventions

Organisme : NCI NIH HHS
ID : P30 CA016672
Pays : United States
Organisme : NCI NIH HHS
ID : R33 CA204582
Pays : United States
Organisme : American Heart Association-American Stroke Association
ID : 18POST34080345
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA202177
Pays : United States
Organisme : NICHD NIH HHS
ID : K25 HD097288
Pays : United States
Organisme : NCI NIH HHS
ID : U54 CA210173
Pays : United States
Organisme : NIH HHS
ID : S10 OD020007
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA183804
Pays : United States

Informations de copyright

Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).

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Auteurs

Emily O Wisniewski (EO)

Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
Johns Hopkins Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD 21218, USA.
ORCID: 0000-0002-4299-4061

Panagiotis Mistriotis (P)

Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
Johns Hopkins Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD 21218, USA.
Department of Chemical Engineering, Auburn University, Auburn, AL 36849, USA.
ORCID: 0000-0002-8069-3278

Kaustav Bera (K)

Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
Johns Hopkins Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD 21218, USA.
ORCID: 0000-0002-0962-4368

Robert A Law (RA)

Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
Johns Hopkins Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD 21218, USA.

Jitao Zhang (J)

Fischell Department of Bioengineering, University of Maryland, College Park, MD 20742, USA.
ORCID: 0000-0002-6240-0371

Milos Nikolic (M)

Fischell Department of Bioengineering, University of Maryland, College Park, MD 20742, USA.
Maryland Biophysics Program, Institute for Physical Science and Technology, University of Maryland, College Park, MD 20742, USA.
ORCID: 0000-0002-1206-1797

Michael Weiger (M)

Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
ORCID: 0000-0003-0724-9565

Maria Parlani (M)

Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
ORCID: 0000-0002-2901-5527

Soontorn Tuntithavornwat (S)

Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
Johns Hopkins Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD 21218, USA.

Alexandros Afthinos (A)

Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
Johns Hopkins Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD 21218, USA.
Department of Neurology, Johns Hopkins University, Baltimore, MD 21287, USA.
ORCID: 0000-0001-6906-0771

Runchen Zhao (R)

Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
Johns Hopkins Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD 21218, USA.
ORCID: 0000-0001-8673-3990

Denis Wirtz (D)

Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
Johns Hopkins Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD 21218, USA.
Johns Hopkins Physical Sciences Oncology Center, Johns Hopkins University, Baltimore, MD 21218, USA.
Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
Department of Oncology, Johns Hopkins University, Baltimore, MD 21205, USA.
ORCID: 0000-0001-6147-3045

Petr Kalab (P)

Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
ORCID: 0000-0002-8145-7728

Giuliano Scarcelli (G)

Fischell Department of Bioengineering, University of Maryland, College Park, MD 20742, USA.
ORCID: 0000-0002-1736-077X

Peter Friedl (P)

Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Department of Cell Biology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, Netherlands.
Cancer Genomics Centre, 3584 Utrecht, Netherlands.
ORCID: 0000-0002-0119-4041

Konstantinos Konstantopoulos (K)

Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
Johns Hopkins Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD 21218, USA.
Johns Hopkins Physical Sciences Oncology Center, Johns Hopkins University, Baltimore, MD 21218, USA.
Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
Department of Oncology, Johns Hopkins University, Baltimore, MD 21205, USA.
ORCID: 0000-0003-2623-1459

Classifications MeSH