Mechanics of the nucleus in cancer cells
The mechanical properties of the nucleus are critical for cell mechanics, in particular when a cell migrates in a confined environment and has to squeeze its nucleus to move through narrow pores. Cancer cells invade the surrounding tissues and can migrate long distances from the primary tumor. To facilitate this process, cells are thought to modify their mechanical properties and in particular nuclear stiffness. The project aims at testing this hypothesis by correlating
rheological measurements of the nucleus of cancer cells with their
invasive properties.
The candidate will focus on
glioblastomas, the most aggressive form of brain tumors, using patient-derived cells form a glioblastoma bank (HGCC, University of Uppsala). First, the
morphology and dynamics of the nucleus will be compared in the selected patient-derived cells. Next, several
biophysical techniques will be applied to measure the
rheological and mechanosensing properties of the nucleus in living cells or of isolated nuclei: intracellular optical tweezers, microplate rheometry, migration through microchannels, and cell stretching. Theoretical
models (visco-elastic, power-law rheology, Hertz model) will be developed to analyze the data. Finally, the mechanical measurements will be correlated with the aggressiveness of the tumor estimated from the glioblastoma bank data (patient survival, proliferation, migration and invasion) and with the expression of genes associated with nuclear mechanics by
bioinformatics approaches.
This project combines micromanipulation and live cell imaging to address both fundamental questions on mechanotransduction and clinical issues related to the diagnostic of glioblastoma by mechanical phenotyping.
Key words: optical tweezers, micropatterning, microfluidics, microplate rheometer, cell stretcher, bioinformatics, patient-derived cells, glioblastoma, microarray analysis, super resolution microscopy, correlative light-electron microscopy
Collaborators: Sandrine Etienne-Manneville (Institut Pasteur, Paris), Atef Asnacios (MSC, Paris Diderot), Mathieu Piel (Institut Curie, Paris), Sinan Haliyo (ISIR, Paris), Karin Forsberg-Nilsson (University of Uppsala, Sweden)
Laboratory: Cell Biology and Cancer, UMR 144 CNRS-Institut Curie, 12 rue Lhomond, 75005 Paris
Contact: Jean-Baptiste Manneville (Jean-Baptiste.Manneville@curie.fr)
Publications:
• D. Guet, K. Mandal, M. Pinot, J. Hoffmann, Y. Abidine, W. Sigaut, S. Bardin, K. Schauer, B. Goud, J.-B. Manneville, Current Biol. 24 1700-11 (2014)
• K. Mandal, A. Asnacios, B. Goud, J.-B. Manneville, Proc Natl Acad Sci U S A 113 E7159-E7168 (2016)
• C. Alibert, B. Goud, J.-B. Manneville, Biol. Cell 109 167-189 (2017)
• S. Mathieu, J.-B. Manneville, Curr Opin Cell Biol. 56 34-44 (2018)
• P. Romani, I.Brian, G. Santinon, A. Pocaterra, M. Audano, S. Pedretti, S. Mathieu, M. Forcato, S. Bicciato, J.-B. Manneville, N. Mitro and S. Dupont, Nature Cell. Biol. 21 338-347 (2019)
• L. Duciel, O. Anezo, K. Mandal, C. Laurent, N. Planque, F. Coquelle J.-B. Manneville, S. Saule, Scientific Reports 9 2990 (2019)
• K. Mandal, K. Pogoda, S. Nandi, S. Mathieu, A. Kasri, E. Klein, F. Radvanyi, B. Goud, P. Janmey, J.-B. Manneville, Nano Letters (2019)