Mechanotransduction of fluid stresses governs 3D cell migration
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Polacheck-2014-Mechanotransduction.pdf
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Author(s)
Polacheck, William J.
German, Alexandra E.
Mammoto, Akiko
Ingber, Donald E.
Kamm, Roger Dale
Date Issued
February 2014
Journal
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences (U.S.)
Citation
Polacheck, W. J., A. E. German, A. Mammoto, D. E. Ingber, and R. D. Kamm. “Mechanotransduction of Fluid Stresses Governs 3D Cell Migration.” Proceedings of the National Academy of Sciences 111, no. 7 (February 3, 2014): 2447–2452.
Version
Final published version
Abstract
Solid tumors are characterized by high interstitial fluid pressure, which drives fluid efflux from the tumor core. Tumor-associated interstitial flow (IF) at a rate of ∼3 µm/s has been shown to induce cell migration in the upstream direction (rheotaxis). However, the molecular biophysical mechanism that underlies upstream cell polarization and rheotaxis remains unclear. We developed a microfluidic platform to investigate the effects of IF fluid stresses imparted on cells embedded within a collagen type I hydrogel, and we demonstrate that IF stresses result in a transcellular gradient in β1-integrin activation with vinculin, focal adhesion kinase (FAK), FAK[superscript PY397], F actin, and paxillin-dependent protrusion formation localizing to the upstream side of the cell, where matrix adhesions are under maximum tension. This previously unknown mechanism is the result of a force balance between fluid drag on the cell and matrix adhesion tension and is therefore a fundamental, but previously unknown, stimulus for directing cell movement within porous extracellular matrix.
MIT Department
Harvard University--MIT Division of Health Sciences and Technology
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Mechanical Engineering
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DOI of Published Version
https://doi.org/10.1073/pnas.1316848111
