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Cells on the Move

10/30/2014
Kelly Rae Chi

Cells can migrate through tight spaces without help from actin or the other usual suspects. Find out how.


Water flow through a cell can propel it through tight spaces within the body, a new study shows (1). The key elements of this so-called “osmotic engine” are sodium-hydrogen ions, water, and cell membrane water channels called aquaporins.

In 2012, Konstantinos Konstantopoulos, a professor of chemical and biomolecular engineering, and his colleagues at Johns Hopkins University in Baltimore, Maryland, found that breast cancer cells moved through narrow channels even when actin polymerization and other major mechanisms of motility were blocked (2). That was surprising, and at the time, “there was no mechanistic interpretation on how cells can move inside those narrow channels,” said Konstantopoulos.

Past methods for studying cancer cell migration involved plating the cells on unconfined surfaces, making it difficult to isolate the mechanism of motility. But in their new study published in Cell, Konstantopoulos’ group used a microchannel device they previously developed to confine a cell within a narrow channel. The researchers then selectively altered osmolarity at the cell’s leading or trailing edges.

According to a mathematical model developed by Sean Sun, the group’s mechanical engineer, for water-based movement to occur, the cell needed an enrichment of ion channels and water pumps at its leading edge. Indeed, when cancer cells lacking those elements were examined, they migrated more slowly. The researchers were also able to alter the direction of migration by changing the osmotic pressures outside the cell.

“The findings of Konstantopoulos and colleagues are certainly thought-provoking and will no doubt prompt many groups to measure water permeation properties of their tissue and cell systems,” noted Dennis Discher, professor of chemical and biomolecular engineering at the University of Pennsylvania in Philadelphia, who was not involved with the work.

Because other research on cells migrating in unconfined environments show that if you inhibit acquaporins you interfere with unconfined 2-D migration, “my bet is that water permeation plays a role… in pretty much in every setting,” Konstantopoulos added.

The group is now working to refine their understanding of confined migration—for example, investigating how vesicle transport inside a cell affects its movement. They also hope to understand how cells enter into narrow channels, Konstantopoulos said.

References

1. Stroka, K.M., Jiang, H., Chen, S.H., Tong, Z., Wirtz, D., Sun, S.X., Konstantopoulos, K. (2014) Water permeation drives tumor cell migration in confined microenvironments. Cell. 157(3), 611-623. doi: 10.1016/j.cell.2014.02.052

2. Balzer, E.M., Tong, Z., Paul, C.D., Hung, W.C., Stroka, K.M., Boggs, A.E., Martin,

S.S., and Konstantopoulos, K. (2012). Physical confinement alters tumor

cell adhesion and migration phenotypes. FASEB J. 26, 4045–4056.