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Physics of single cell mechanosensing

MSC : Jonathan Fouchard, Pauline Durand, Démosthène Mitrossilis, Alain Richert, Atef Asnacios.

Collaborations : Michel Saint-Jean (MSC), Maïté Coppey (IJM), Ben Fabry (Université Erlangen), Qi-Chang He (Université Marne-la-Vallée), Patrick Vicart (P7), Assaf Zemel (Université Jerusalem), Jocelyn Etienne (LSP, Grenoble), Alexis Peaucelle (INRA, Versailles), Olivier Hamant (ENS, Lyon), Siobhan Braybrook (Université Bern).

Many mechanical cues, such as forces and the rigidity of living tissues, control the biological functions and fate of living cells. In particular, substrate rigidity was shown to direct cell spreading, migration, and stem cell differentiation. Our aim is to understand the physical processes allowing cells to detect and adapt to the rigidity of its environment. Thus, we develop original setups combining single cell mechanical measurements (rheometry, traction force, [1]) and visualization of the evolution of the cell structure (cell shape in phase contrast, stress fibers in confocal microscopy, and adhesion complexes in TIRFM). On the one hand,we could characterize single cell response to a constant load (creep function, [2]). This response, measured at the whole cell scale ( 10 µm), was identical to local behavior (30 nm-2µm) suggesting a self-similar model of cell mechanics [3]. On the other hand, we measured single cell traction forces and mechanical power generation, showing that cell adaptation to the stiffness of its environment exhibits features of acto-myosin contractility [4]. We have also designed a unique method allowing us to determine the real-time single cell response to a sudden change (t<0.1 s) in the stiffness of its environment [5]. We could thus show that cell contractility was instantaneously adapted to stiffnes [6], suggesting that initial sensing could be mechanical in nature. This fast cell-scale response could coordinate local (longer time scale) activity of focal adhesions, giving rise to a model of initial cell polarization [7]. We are currently trying to concile features of cell rheology and adaptation to stiffness in order to draw a consistent picture of a mechanical process of rigidity sensing [8]. Eventually, we are initiating experiments on mechanosensing in plant cells to investigate their specific strategies to adapt to their mechanical environment.

- [1] Desprat et al., Rev. Sci. Instrum., 2006
- [2] Desprat et al., Biophys. J., 2005
- [3] Balland et al., PRE, 2006
- [4] Mitrossilis et al., PNAS, 2009
- [5] Mitrossilis et al., European Patent, 2009
- [6] Mitrossilis et al., PNAS, 2010
- [7] Fouchard et al., Cell Adhes. Migr., 2010
- [8] Monteiro et al., Biomech. Model. Mechanobiol., submitted

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