Mechanotransduction of fluid stresses governs 3D cell migration
Polacheck, William J.
German, Alexandra E.
Ingber, Donald E.
Kamm, Roger D.
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CitationPolacheck, W. J., A. E. German, A. Mammoto, D. E. Ingber, and R. D. Kamm. 2014. “Mechanotransduction of Fluid Stresses Governs 3D Cell Migration.” Proceedings of the National Academy of Sciences 111 (7): 2447–52. https://doi.org/10.1073/pnas.1316848111.
AbstractSolid 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 similar to 3 mu m/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 beta 1-integrin activation with vinculin, focal adhesion kinase (FAK), FAK(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.
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