Editors' ChoiceCell Migration

Tension at the Leading Edge

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Science Signaling  24 Jan 2012:
Vol. 5, Issue 208, pp. ec28
DOI: 10.1126/scisignal.2002881

During migration, cells adopt a polarized morphology in which protrusions and actin polymerization, which are driven by the guanosine triphosphatase Rac, are confined to the leading edge. Maintenance of cell polarity during migration is thought to be a result of feedback mechanisms involving either the accumulation of polarity components at the leading edge or the production at the leading edge of inhibitors that diffuse through the cytosol to prevent the formation of competing cell fronts. Houk et al. performed mathematical modeling and experiments with polarized human neutrophils to test the role of these diffusion-based mechanisms in maintaining cell polarity. In their system, the migrating cell consisted of a cell protrusion or pseudopod at the front, which was connected to the rest of the cell body by a thin cellular tether. When the tether was severed by laser dissection, almost half of the cell bodies formed a new pseudopod, which suggested that inhibitory molecules had not accumulated in the cell body before dissection. FRAP (fluorescence recovery after photobleaching) experiments showed that the tether inhibited the diffusion of green fluorescent protein from the pseudopod to the cell body. Optical trapping experiments showed that the membrane tension at the pseudopod was twice that of the rest of the cell. By applying suction through a micropipette tip in contact with the cell body of a migrating cell, the authors increased membrane tension in the cell body, which resulted in retraction of the pseudopod and inhibition of Rac activity, as measured by total internal reflection fluorescence microscopy. Finally, hypertonic buffer, which decreased membrane tension throughout the cell, expanded the area of the leading edge. Thus, the authors suggest that membrane tension in the leading edge, and not diffusible components, constrains signaling and maintains polarity by inhibiting the formation of other pseudopods.

A. R. Houk, A. Jilkine, C. O. Mejean, R. Boltyanskiy, E. R. Dufresne, S. B. Angenent, S. J. Altschuler, L. F. Wu, O. D. Weiner, Membrane tension maintains cell polarity by confining signals to the leading edge during neutrophil migration. Cell 148, 175–188 (2012). [Online Journal]

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