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

Research output: Contribution to journalArticleResearchpeer-review

227 Citations (Scopus)

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. PaperFlick

Original languageEnglish
Pages (from-to)611-623
Number of pages13
JournalCell
Volume157
Issue number3
DOIs
Publication statusPublished - 24 Apr 2014
Externally publishedYes

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