Urokinase receptor mediates mechanical force transfer across the cell surface.
The tripartite complex formed by the urokinase receptor, urokinase, and its inhibitor is an enzymatic system that controls plasmin formation involved in degradation of extracellular matrix proteins. With the use of magnetic twisting cytometry with urokinase-coated ferromagnetic beads, we applied mechanical stress directly to the urokinase receptor on the surface of human myogenic cells in culture. The stiffness and the stiffening response measured through the urokinase receptor resembled those of integrins, which are linked mechanically to the cytoskeleton. Furthermore, stiffness decreased with disruption of actin microfilaments. These results demonstrate that the urokinase receptor is coupled mechanically to the cytoskeleton. Inhibition of the tripartite complex formation with antibodies led to a twofold increase in cytoskeletal stiffness. A stiffened cytoskeleton might impede cytoskeletal remodeling and reorganization and thus impede cell motility. Our results demonstrate that the urokinase receptor mediates mechanical force transfer across the cell surface. As such, it is a novel pathway to regulate cytoskeletal stiffness and, thereby, possibly to modulate motility of normal and abnormal adherent cells.
Wang
N
N
Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
Planus
E
E
Pouchelet
M
M
Fredberg
J J
JJ
Barlovatz-Meimon
G
G
D002462:Cell Membrane / Q000502:physiology; D003599:Cytoskeleton / Q000502:physiology*; D004548:Elasticity; D006801:Humans; D008280:Magnetics; D008722:Methods; D008863:Microspheres; D009132:Muscles / Q000166:cytology / Q000502:physiology*; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000502:physiology*; D055293:Receptors, Urokinase Plasminogen Activator; D013314:Stress, Mechanical; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
C524898:PLAUR protein, human; D017395:Plasminogen Activator Inhibitor 1; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator