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Accueil du site > Emplois et Stages > Sujets de Thèses > PhD Project : MECHANICAL RESPONSE OF CELLULAR SYSTEMS : Do cells have a sense of touch ?

PhD Project : MECHANICAL RESPONSE OF CELLULAR SYSTEMS : Do cells have a sense of touch ?

Institute :

Laboratoire transdisciplinaire Joliot Curie

PhD supervisor :

Françoise Argoul, DR CNRS

Email adress and phone number :

francoise.argoul(A)ens-lyon.fr, 0472728823

Team members involved :

Alain Arneodo, Benjamin Audit, Lotfi Berguiga, Karine Monier, Fabien Mongelard, Cédric Vaillant

Project description :

Cells respond dynamically to the mechanical and rheological properties of their surrounding. They may even adapt their own internal organization to match the stiffness of the support on which they adhere. The mechanical response of a cell upon the substrate rigidity depends on the tissue type from which the cells are derived [1]. For example, fibroblasts achieve maximal spreading on stiff substrates ( 10 kPa), whereas neurons branch more avidly on softer subtrates (< 0.5 kPa), and chondrocytes only begin to spread at 10 kPa. Matrix stiffness also influences cell proliferation and differentiation ; for instance mesenchymal stem cells can be differentiated into neurogenic, myogenic or osteogenic cell types according to the magnitude of the matrix stiffness, mimicking that of the native tissue [2]. A current hypothesis to explain such a spreading increase on stiffer adhesive surfaces is that by pulling on the matrix at adhesion foci, the cell likely produces tension within its membrane and in the underlying cortical actin mesh. Whereas the role of the focal adhesion loci has been shown by micromechanical stimulation experiments to be highly dynamic and mechanosensitive [3], the echo of these stimulations on 3D cytoskeleton assembly dynamics and nuclear cell core are much less understood.

Thanks to the expertise of the team “Mechanogenetics of the cell” of the Transdisciplinary Joliot Curie Laboratory of ENS LYON, we propose to focus on the interplay of the nuclear mechanical stiffness with the cytoskeleton mediated mechanical response of neuronal cells during their differentiation. We will combine optical microscopy (fluorescence and total internal reflection interference microscopy) together with micromechanical stimulation by atomic force microscopy to tune precisely the mechanical stress and to measure the extracellular matrix rigidity. We will address the following questions. How does the nuclear domain, central to the cell body, organize its surrounding cytoskeleton, in response to a mechanical stress ? Is this hard core of the cell important in the global rigidity of a cell ? How does the remodeling of the nuclear architecture influence retroactively the mechanical property of the cell ? Can we follow in real time the modification of a cell rigidity during its differentiation ? The work will combine biophysical methods based on fluorescence and interferometric microscopies, with cellular biology approaches, and physical modeling.

[1] D.E. Discher, P. Janmey and Y.L. Wang, Tissue cells feel and respond to the stiffness of their substrate. Science, 310, 1139-1143 (2005).

[2] A.J Engler, S. Sen, H.L. Sweeney and D.E. Discher, Matrix elasticity directs stem cell lineage specification, Cell 126, 677-689 (2006).

[3] M. Ghibaudo, J.M. Di Meglio, P. Hersen and B. Ladoux, Mechanics of cell spreading within 3D micropatterned environments, Lab. On Chip, Online nov 2010 : DOI 10.1039/c01c00221f