Intracellular mechanics of migrating fibroblasts.
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 cytoskeleton is essential for directed cell migration and is coordinated through microtubules.
Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
Thomas P
TP
Kole
Yiider
Y
Tseng
Ingjye
I
Jiang
Joseph L
JL
Katz
Denis
D
Wirtz
D016475:3T3 Cells; D000818:Animals; D001920:Bradykinin / Q000378:metabolism; D002465:Cell Movement; D003599:Cytoskeleton / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism*; D005583:Fourier Analysis; D007700:Kinetics; D051379:Mice; D008856:Microscopy, Fluorescence; D008858:Microscopy, Phase-Contrast; D008870:Microtubules / Q000378:metabolism; D015739:Nocodazole / Q000494:pharmacology; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D013997:Time Factors; D014945:Wound Healing; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism; D020744:rac GTP-Binding Proteins / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism
D010982:Platelet-Derived Growth Factor; D020764:cdc42 GTP-Binding Protein; D020744:rac GTP-Binding Proteins; D020741:rho GTP-Binding Proteins; D001920:Bradykinin; D015739:Nocodazole