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Originally published as MBC in Press, 10.1091/mbc.E04-06-0485 on October 13, 2004

Vol. 16, Issue 1, 328-338, January 2005

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Intracellular Mechanics of Migrating Fibroblasts{boxd}

Thomas P. Kole, Yiider Tseng, Ingjye Jiang, Joseph L. Katz, and Denis Wirtz *

Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218

Submitted June 14, 2004; Revised September 28, 2004; Accepted October 1, 2004
Monitoring Editor: Jennifer Lippincott-Schwartz

Cell migration is a highly coordinated process that occurs through the translation of biochemical signals into specific biomechanical events. The biochemical and structural properties of the proteins involved in cell motility, as well as their subcellular localization, have been studied extensively. However, how these proteins work in concert to generate the mechanical properties required to produce global motility is not well understood. Using intracellular microrheology and a fibroblast scratch-wound assay, we show that cytoskeleton reorganization produced by motility results in mechanical stiffening of both the leading lamella and the perinuclear region of motile cells. This effect is significantly more pronounced in the leading edge, suggesting that the mechanical properties of migrating fibroblasts are spatially coordinated. Disruption of the microtubule network by nocodazole treatment results in the arrest of cell migration and a loss of subcellular mechanical polarization; however, the overall mechanical properties of the cell remain mostly unchanged. Furthermore, we find that activation of Rac and Cdc42 in quiescent fibroblasts elicits mechanical behavior similar to that of migrating cells. We conclude that a polarized mechanics of the cytoskelton is essential for directed cell migration and is coordinated through microtubules.

Article published online ahead of print. Mol. Biol. Cell 10.1091/mbc.E04-06-0485. Article and publication date are available at www.molbiolcell.org/cgi/doi/10.1091/mbc.E04-06-0485.

{boxd} The online version of this article contains supplemental material at MBC Online (http://www.molbiolcell.org).

* Corresponding author. E-mail address: wirtz{at}jhu.edu.




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