Fig. 6. Proposed mechanism of interstitial flow-driven myofibroblast differentiation and matrix remodeling. First, flow itself can impose shear stress on the cells directly and strain on the cells via stresses on the ECM fibers to which the cells attach. Either of these may trigger TGF-ß₁ expression, the latter through ₁ß₁ integrin signaling. TGF-ß₁ drives -SMA expression as the fibroblasts differentiate into myofibroblasts and align the matrix fibers.