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Urokinase receptor mediates mechanical force transfer across the cell surface
N Wang1, E Planus, M Pouchelet
1Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
The American Journal of Physiology
|April 1, 1995
Summary
The urokinase receptor mechanically links to the cell cytoskeleton, influencing cell stiffness and motility. This discovery reveals a new pathway for regulating cell movement through mechanical force transfer.
Area of Science:
- Cell biology
- Biophysics
- Biochemistry
Background:
- The urokinase receptor (uPAR) forms a complex with urokinase and its inhibitor, controlling plasmin formation and extracellular matrix degradation.
- Integrins are known to mechanically link to the cytoskeleton, influencing cell mechanics.
Purpose of the Study:
- To investigate the mechanical coupling of the urokinase receptor to the cytoskeleton.
- To determine if the urokinase receptor can mediate mechanical force transfer across the cell surface.
Main Methods:
- Magnetic twisting cytometry was used to apply mechanical stress to urokinase receptors on human myogenic cells.
- Actin microfilaments were disrupted to assess their role in urokinase receptor-mediated stiffness.
- Antibodies were used to inhibit tripartite complex formation.
Main Results:
- Urokinase receptor stiffness and stiffening response mimicked that of integrins.
- Cell stiffness decreased upon disruption of actin microfilaments, indicating cytoskeletal coupling.
- Inhibition of tripartite complex formation resulted in a twofold increase in cytoskeletal stiffness.
- The urokinase receptor was shown to mediate mechanical force transfer across the cell surface.
Conclusions:
- The urokinase receptor is mechanically coupled to the cytoskeleton.
- This coupling provides a novel pathway for regulating cytoskeletal stiffness and cell motility.
- Modulation of urokinase receptor-mediated mechanical forces may impact normal and abnormal cell movement.