Mechanotransduction of fluid stresses governs 3D cell migration

作者：Polacheck William J; German Alexandra E; Mammoto Akiko; Ingber Donald E; Kamm Roger D^*

来源：Proceedings of the National Academy of Sciences, 2014, 111(7): 2447-2452.

DOI：10.1073/pnas.1316848111

• mechanobiology
• breast cancer
• metastasis

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 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.

• 出版日期2014-2-18