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Proc Natl Acad Sci U S A. 2014 Feb 18;111(7):2447-52. doi: 10.1073/pnas.1316848111. Epub 2014 Feb 3.

Mechanotransduction of fluid stresses governs 3D cell migration.

Author information

1
Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139.

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(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.

KEYWORDS:

breast cancer; mechanobiology; metastasis

PMID:
24550267
PMCID:
PMC3932905
DOI:
10.1073/pnas.1316848111
[Indexed for MEDLINE]
Free PMC Article

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