title: Water permeation drives tumor cell migration in confined microenvironments.
abstract: Cell migration is a critical process for diverse (patho)physiological phenomena. Intriguingly, cell migration through physically confined spaces can persist even when typical hallmarks of 2D planar migration, such as actin polymerization and myosin II-mediated contractility, are inhibited. Here, we present an integrated experimental and theoretical approach ("Osmotic Engine Model") and demonstrate that directed water permeation is a major mechanism of cell migration in confined microenvironments. Using microfluidic and imaging techniques along with mathematical modeling, we show that tumor cells confined in a narrow channel establish a polarized distribution of Na+/H+ pumps and aquaporins in the cell membrane, which creates a net inflow of water and ions at the cell leading edge and a net outflow of water and ions at the trailing edge, leading to net cell displacement. Collectively, this study presents an alternate mechanism of cell migration in confinement that depends on cell-volume regulation via water permeation.
authors.affiliation: Johns Hopkins Institute for NanoBioTechnology, The Johns Hopkins University, Baltimore, MD 21218, USA; Johns Hopkins Physical Sciences-Oncology Center, The Johns Hopkins University, Baltimore, MD 21218, USA; Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, MD 21218, USA.
authors.forename: Kimberly M
authors.initials: KM
authors.lastname: Stroka
authors.affiliation: Department of Mechanical Engineering, The Johns Hopkins University, Baltimore, MD 21218, USA; CAS Key Laboratory of Mechanical Behavior and Design of Materials, University of Science and Technology of China, Hefei, Anhui 230026, PRC.
authors.forename: Hongyuan
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, MD 21218, USA.
authors.forename: Shih-Hsun
authors.initials: SH
authors.lastname: Chen
authors.affiliation: Johns Hopkins Institute for NanoBioTechnology, The Johns Hopkins University, Baltimore, MD 21218, USA; Johns Hopkins Physical Sciences-Oncology Center, The Johns Hopkins University, Baltimore, MD 21218, USA; Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, MD 21218, USA.
authors.forename: Ziqiu
authors.initials: Z
authors.lastname: Tong
authors.affiliation: Johns Hopkins Institute for NanoBioTechnology, The Johns Hopkins University, Baltimore, MD 21218, USA; Johns Hopkins Physical Sciences-Oncology Center, The Johns Hopkins University, Baltimore, MD 21218, USA; Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, MD 21218, USA.
authors.forename: Denis
authors.initials: D
authors.lastname: Wirtz
authors.affiliation: Johns Hopkins Institute for NanoBioTechnology, The Johns Hopkins University, Baltimore, MD 21218, USA; Johns Hopkins Physical Sciences-Oncology Center, The Johns Hopkins University, Baltimore, MD 21218, USA; Department of Mechanical Engineering, The Johns Hopkins University, Baltimore, MD 21218, USA; Department of Biomedical Engineering, The Johns Hopkins University, Baltimore, MD 21218, USA. Electronic address: ssun@jhu.edu.
authors.forename: Sean X
authors.initials: SX
authors.lastname: Sun
authors.affiliation: Johns Hopkins Institute for NanoBioTechnology, The Johns Hopkins University, Baltimore, MD 21218, USA; Johns Hopkins Physical Sciences-Oncology Center, The Johns Hopkins University, Baltimore, MD 21218, USA; Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, MD 21218, USA; Department of Biomedical Engineering, The Johns Hopkins University, Baltimore, MD 21218, USA. Electronic address: konstant@jhu.edu.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Konstantopoulos
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D051402:Aquaporin 5 / Q000378:metabolism; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D002465:Cell Movement; D048429:Cell Size; D006801:Humans; D051379:Mice; D008954:Models, Biological; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism; D014867:Water
chemical_list: D000199:Actins; D051402:Aquaporin 5; D017923:Sodium-Hydrogen Exchangers; D014867:Water
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