Mechanotransduction of fluid stresses governs 3D cell migration

• DOI: 10.1073/pnas.1316848111
• Publication Date: 2014-02-04T06:33:35Z
• Authors: William J. Polacheck; Alexandra E. German; Akiko Mammoto; Donald E. Ingber; Roger D. Kamm
• Keywords: 0301 basic medicine; 570; Focal Adhesions; Integrin beta1; Green Fluorescent Proteins; Extracellular Fluid; Transfection; Mechanotransduction, Cellular; Models, Biological; Vinculin; Extracellular Matrix; 03 medical and health sciences; Cell Movement; Cell Line, Tumor; Hydrodynamics; Humans; RNA, Small Interfering

Significance Interstitial flow (IF) is elevated in solid tumors and imparts fluid stresses on tumor cells within the extracellular matrix (ECM), and these fluid stresses must be balanced by stress in matrix adhesions to maintain static equilibrium. This force balance results in greater matrix adhesion tension on the upstream side of the cell, and we demonstrate that this tension activates β1-integrin adhesion complexes, resulting in localization and activation of focal adhesion (FA) proteins near the upstream membrane. Importantly, we demonstrate that this asymmetric FA activation governs the direction of cell migration in 3D, and therefore our data show that mechanical stress acting on cells within a 3D ECM is a fundamental directional migratory stimulus.