Water permeation drives tumor cell migration in confined microenvironments

Kimberly M Stroka; Hongyuan Jiang; Shih-Hsun Chen; Ziqiu Tong; Denis Wirtz; Sean X Sun; Konstantinos Konstantopoulos

doi:10.1016/j.cell.2014.02.052

Water permeation drives tumor cell migration in confined microenvironments

Cell. 2014 Apr 24;157(3):611-23. doi: 10.1016/j.cell.2014.02.052. Epub 2014 Apr 10.

Authors

Kimberly M Stroka¹, Hongyuan Jiang², Shih-Hsun Chen³, Ziqiu Tong¹, Denis Wirtz¹, Sean X Sun⁴, Konstantinos Konstantopoulos⁵

Affiliations

¹ 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.
² 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.
³ Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, MD 21218, USA.
⁴ 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.
⁵ 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.

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.

Publication types

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

MeSH terms

Actins / metabolism
Animals
Aquaporin 5 / metabolism
Cell Line, Tumor
Cell Membrane / metabolism
Cell Movement*
Cell Size
Humans
Mice
Models, Biological*
Sodium-Hydrogen Exchangers / metabolism
Water*

Substances

Actins
Aquaporin 5
Sodium-Hydrogen Exchangers
Water

Abstract

Publication types

MeSH terms

Substances

Grants and funding