Microrheological properties of cancer cells

Cancer cells interact with the endothelium during cell transmigration, which is a key step in cancer metastasis. When cancer cells adhere to endothelium cells, they use receptors (integrins, etc.) which are mechanosensors transmitting mechanical forces from the outside to the inside of the cell and vice-versa [1]. These mechanosensors allow to sense the environment, to respond to environment changes or to modify this environment. Cells are able to modify their morphology, their focal adhesion structures, their cytoskeleton and their migrating behavior as a function of the environment. Conversely, cells can modify the outside environment organisation or rigidity : it has been shown that in some breast cancers, the extra-cellular matrix is more rigid close to the tumor. In addition some cells have the ability to remodel the nearby extracellular matrix [2].
The PhD program proposed here is about the mechanical properties characterization of plated cancer cells as they are submitted to external stresses. These measurements will then be compared with measurements done on cancer cells in contact with endothelial cells, to investigate the effect of such an environment. Dynamic measurements will be made with an AFM (JPK Instruments, on an inverted microscope) using the force modulation mode : when in contact with a cell, the tip will be oscillated at a given frequency and signal will be recorded. Amplitude and phase of the signal will give access to the elastic (G') and loss modulus (G''), as a function of frequency, thanks to Hertz modified model. A recent development of this software have been carried out in our group [3].
First experiments carried out on live cells give data comparable to the literature [4]. This method is a quite new one and has never been tested on cancer cells. We suggest to investigate different cancer cells with various invasiveness, in contact with different environments.

Collaboration: This work is carried out in collaboration with biologists at Intitut Albert Bonniot in Grenoble.

References:
[1] O. Haddad, R. Chotard-Ghodsnia, C. Verdier and A. Duperray, Tumor cell/endothelial cell tight contact upregulates endothelial adhesion molecule expression mediated by NFkB: differential role of the shear stress, Exp. Cell Research, 316, 615-626 (2010)
[2] A. Iordan, A. Duperray, A. Gérard, A. Grichine and C. Verdier, Breakdown of cell-collagen networks through collagen remodeling, Biorheology, 47, 277-295 (2010)
[3] A. Yusuf, From static to dynamic rheological measurements using AFM, stage M2 Mécanique, 2011
[4] J. Alcaraz, L. Buscemi, M. Grabulosa, X. Trepat, B. Fabry, R.Farré and D. Navajas, Biophys. J., 84, 2071-2079 (2003)

Candidates with a background in biomechanics/biophysics should apply with a CV and letter of intention (letters of recommendation welcome) to:

Valérie LAURENT – Claude VERDIER
valerie.laurent@ujf-grenoble.fr
claude.verdier@ujf-grenoble.fr

Laboratoire Interdisciplinaire de Physique
140 rue de la Physique - BP87
38402 Saint Martin d'Hères cedex
http://www-lsp.ujf-grenoble.fr/equip...ier/index.html