Mechanotransduction of fluid stresses governs 3D cell migration

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Cell Line, Tumor
  • Cell Movement / physiology*
  • Extracellular Fluid / metabolism*
  • Extracellular Matrix / metabolism*
  • Focal Adhesions / physiology
  • Green Fluorescent Proteins
  • Humans
  • Hydrodynamics*
  • Integrin beta1 / metabolism
  • Mechanotransduction, Cellular / physiology*
  • Models, Biological*
  • RNA, Small Interfering / genetics
  • Transfection
  • Vinculin


  • Integrin beta1
  • RNA, Small Interfering
  • Vinculin
  • Green Fluorescent Proteins