Project title: Interplay of cellular forces, adhesion and mechanics during colorectal cancer

Type of rotation: M2 (6 months)
Supervisors: Claire Valotteau (LAI) and Elsa Bazellières (IBDM)

Concept & Objectives

During cancer progression, epithelial tissues undergo several changes. The surrounding extracellular matrix stiffens, while cancer cells loosen their intercellular adhesions and soften. How exactly intrinsic cellular force generation and cell-cell adhesion strength are coupled to cancer cell mechanics adaptation remain elusive. Within this project, we will study how colorectal epithelia with different genetic background adapt their epithelial organization, stiffnesses and forces in 3D model systems. These results will be compared with observations made on circulating tumor cells derived from patient with colorectal cancer, mimicking a more advanced stage of cancer progression.

The intern will develop skills in cell biology (cell culture, immunofluorescence, confocal imaging) and will be trained to use advanced biophysical tools (deformable hydrogel beads, atomic force microscopy).

This project may be continued as a PhD thesis.

References

Gensbittel, V., Kräter, M., Harlepp, S., Busnelli, I., Guck, J., & Goetz, J. G. (2021). Mechanical adaptability of tumor cells in metastasis. Developmental cell, 56(2), 164-179.


Träber, K. Uhlmann, S. Girardo, G. Kesavan, K. Wagner, J. Friedrichs, R. Goswami, K. Bai, M. Brand, C. Werner, D. Balzani & J. Guck (2019). Polyacrylamide Bead Sensors for in vivo Quantifcation of Cell-Scale Stress in Zebrafsh Development. Scientific Reports 9:17031


Valentina Palmieri, Donatella Lucchetti, Alessandro Maiorana, Massimiliano Papi, Giuseppe Maulucci, Gabriele Ciasca, Maria Svelto, Marco De Spirito, and Alessandro Sgambato. Biomechanical investigation of colorectal cancer cells. Applied Physics Letters 105, 123701 (2014)