UROKINASE RECEPTOR MEDIATES MECHANICAL FORCE TRANSFER ACROSS THE CELL-SURFACE

The tripartite complex formed by the urokinase receptor, urokinase, an d its inhibitor is an enzymatic system that controls plasmin formation involved in degradation of extracellular matrix proteins. With the us e of magnetic twisting cytometry with urokinase-coated ferromagnetic b eads, we applied mechanical stress directly to the urokinase receptor on the surface of human myogenic cells in culture. The stiffness and t he stiffening response measured through the urokinase receptor resembl ed those of integrins, which are linked mechanically to the cytoskelet on. Furthermore, stiffness decreased with disruption of actin microfil aments. These results demonstrate that the urokinase receptor is coupl ed mechanically to the cytoskeleton. Inhibition of the tripartite comp lex formation with antibodies led to a twofold increase in cytoskeleta l stiffness. A stiffened cytoskeleton might impede cytoskeletal remode ling and reorganization and thus impede cell motility. Our results dem onstrate that the urokinase receptor mediates mechanical force transfe r across the cell surface. As such, it is a novel pathway to regulate cytokeletal stiffness and, thereby, possibly to modulate motility of n ormal and abnormal adherent cells.