Description du sujet de thèse

Cell motility refers to the spontaneous displacement of cells. This cell function has consequences for human wellbeing (wound healing) or unhealthiness (cancer metastasis). Cells in the body migrate in a confined environment where cells are able to actively pass through constrictions smaller than their nuclei. Because the nucleus is the stiffest cell organelle, at first sight, it could limit the efficiency of confined cell motility. This is not the case, since the nucleus deforms under the effect of active cytoskeletal forces that pull and push the nucleus through constrictions. Another observation of cells migrating in confined spaces is that their membrane deforms into blebs that grow and shrink under the effect of cytoskeleton dynamic self-assembly, and these blebs correlate with cell translocation. These two observations points to an active process of nucleus translocation that this project aims at unveiling. Because an increase in cell motility is a hallmark of cancer metastasis, it is crucial to understand how this activation occurs.

This thesis project consists in using controlled microfluidic experimental systems that mimic the physiological situation of confined cell motility and follow how the cell membrane, the cytoskeleton and the nucleus re-arrange as a function of time, space, and constriction size. Optical microscopy will be used to follow cells migrating through constrictions. Experiments will be analysed through statistical physics methods and compared to models of cell motility and nuclear translocation that will apply to cell and nuclei trajectories, including observables such as cellular, cytoskeletal, and nuclear shape changes.

A collaboration with theoretical physicists within the LPENS (Thierry Mora, Aleksandra Walczak and Vincent Hakim) will allow for a close-to-data analysis. This project relies on a collaboration with the translational department of Institut Curie, who are specialists of metastatic cell state and transition. Moreover, this project is in a context of a collaborative project with Alain Karma and Herbert Levine from Northeastern University USA.

Contexte de travail

experimental theme, with a strong theoretical/analytical component

Contraintes et risques

collaborations with Institut Curie