Real-time single-cell response to stiffness

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 107; no. 38; pp. 16518 - 16523
• Main Authors: Mitrossilis, Démosthène, Fouchard, Jonathan, Pereira, David, Postic, François, Richert, Alain, Saint-Jean, Michel, Asnacios, Atef
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 21.09.2010; National Acad Sciences
• Subjects: Animals; Biological Sciences; Biophysical Phenomena; Biosensors; Cell adhesion & migration; Cell Adhesion - physiology; Cell Line; Cell lines; Cells; Deformation; Elasticity - physiology; Electrostatics; Epithelial cells; Extracellular Matrix - physiology; Fibronectins - physiology; Gels; Mechanotransduction, Cellular - physiology; Methods; Mice; Morphology; Muscle Fibers, Skeletal - physiology; Parallel plates; Physical Sciences; Real time; Signal Transduction - physiology; Static Electricity; Stem cells; Stiffness; Stress, Mechanical; Structural deflection
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1007940107

Living cells adapt to the stiffness of their environment. However, cell response to stiffness is mainly thought to be initiated by the deformation of adhesion complexes under applied force. In order to determine whether cell response was triggered by stiffness or force, we have developed a unique method allowing us to tune, in real time, the effective stiffness experienced by a single living cell in a uniaxial traction geometry. In these conditions, the rate of traction force buildup dF/dt was adapted to stiffness in less than 0.1 s. This integrated fast response was unambiguously triggered by stiffness, and not by force. It suggests that early cell response could be mechanical in nature. In fact, local force-dependent signaling through adhesion complexes could be triggered and coordinated by the instantaneous cell-scale adaptation of dF/dt to stiffness. Remarkably, the effective stiffness method presented here can be implemented on any mechanical setup. Thus, beyond single-cell mechanosensing, this method should be useful to determine the role of rigidity in many fundamental phenomena such as morphogenesis and development.