TY - JOUR
T1 - Water permeation drives tumor cell migration in confined microenvironments
AU - Stroka, Kimberly M.
AU - Jiang, Hongyuan
AU - Chen, Shih Hsun
AU - Tong, Ziqiu
AU - Wirtz, Denis
AU - Sun, Sean X.
AU - Konstantopoulos, Konstantinos
N1 - Funding Information:
We thank Jean Paul Thiery for providing S180 cells, Antonio LLombart-Bosch for CH2879 cells, Ramana Sidhaye for AQP5 siRNA adenovirus, and Helim Aranda-Espinoza for use of the Micro-Osmometer. This work was supported by awards from the National Science Foundation (NSF-1159823 to K.K.), the National Cancer Institute (U54-CA143868 to D.W., K.K., and S.X.S.; RO1GM075305 to S.X.S.; RO1CA174388 to D.W.; T32-CA130840 to K.M.S.; and F32-CA177756 to K.M.S.), the Kleberg Foundation (to K.K. and S.X.S.), and the National Natural Science Foundation of China (NSFC 11342010 to H.J.).
PY - 2014/4/24
Y1 - 2014/4/24
N2 - 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
AB - 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
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U2 - 10.1016/j.cell.2014.02.052
DO - 10.1016/j.cell.2014.02.052
M3 - Article
C2 - 24726433
AN - SCOPUS:84899623190
SN - 0092-8674
VL - 157
SP - 611
EP - 623
JO - Cell
JF - Cell
IS - 3
ER -