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Intracellular fluid flow in rapidly moving cells


Cytosolic fluid dynamics have been implicated in cell motility1,2,3,4,5 because of the hydrodynamic forces they induce and because of their influence on transport of components of the actin machinery to the leading edge. To investigate the existence and the direction of fluid flow in rapidly moving cells, we introduced inert quantum dots into the lamellipodia of fish epithelial keratocytes and analysed their distribution and motion. Our results indicate that fluid flow is directed from the cell body towards the leading edge in the cell frame of reference, at about 40% of cell speed. We propose that this forward-directed flow is driven by increased hydrostatic pressure generated at the rear of the cell by myosin contraction, and show that inhibition of myosin II activity by blebbistatin reverses the direction of fluid flow and leads to a decrease in keratocyte speed. We present a physical model for fluid pressure and flow in moving cells that quantitatively accounts for our experimental data.

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Figure 1: Single-particle tracking of QDs in the lamellipodia of live keratocytes.
Figure 2: Flow-induced size-dependent distribution of probes.
Figure 3: Measurements of fluid flow based on the distribution of 655QDs.
Figure 4: Effects of blebbistatin on fluid flow.

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We thank Theresa Harper and Marcel Bruchez from Quantum Dot Corporation (Molecular Probes, Invitrogen) for providing the quantum dot probes; W.E. Moerner for advice on the single-particle tracking experiments; Paul Wiseman, Ben Hebert and Lia Gracey for their contributions to the initial phase of this project; Michael Saxton and Cyrus Wilson for useful discussions; and Boris Slepchenko for help with Virtual Cell. K.K. was supported by a Damon Runyon Postdoctoral Fellowship, a Horev fellowship from the Technion, an Allon Fellowship from the Israel Council for Higher Education, and by grants from the Morasha Program of the Israel Science Foundation, the Converging Technologies Program of The Israel Council for Higher Education, the Wolfson Foundation, and a European Research Council Starting Grant. A.M. was supported by grants from the National Institutes of Health and the National Science Foundation. J.A.T. was supported by grants from the National Institutes of Health, the American Heart Association and the Howard Hughes Medical Institute. P.T.Y. was supported by a Howard Hughes Medical Institute Predoctoral Fellowship and Stanford Graduate Fellowship.

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K.K. and J.A.T. conceived and designed the experiments; K.K. performed the experiments and analysed the data; A.M. and K.K. developed the model; P.T.Y. made the initial observation of enhancement of large probes at the leading edge; A.K. contributed to the single-particle tracking experiments; K.K., A.M., P.T.Y. and J.A.T. discussed the results and wrote the paper.

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Correspondence to Kinneret Keren.

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Keren, K., Yam, P., Kinkhabwala, A. et al. Intracellular fluid flow in rapidly moving cells. Nat Cell Biol 11, 1219–1224 (2009).

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