By Yves Lherry In On April 6, 2017
Study of nucleus deformation by actin cytoskeleton during cell migration in a confined environement.
Immune and cancer cells depend on migration to move through the organism and are able to migrate in various ways. The relevance of the 3D physical chemical and mechanical environement is now recognized, as a cell often needs to migrate between other cells or in an heterogeneous extra-cellular matrix. To emulate cell migration in 3D we will use cell migration through a constriction. The nucleus limits the passage of a cell through a constriction and it is pushed inside with a pressure gradient in the cell. In some cases large deformations of the nucleus are necessary and are accomplished by actin polymerization generating a compressing force and sometimes breaking the nuclear envelop.
Here we aim at understanding in details and quantifying this mechanism but also to propose models for its key components. To accomplish that we propose the use of the super-paramagnetic particles developed at PMMH and microfluidics techniques from Institut Curie. Three kinds of experiments will be carried out : Actin polymerization under confinement (induced actin polymerization between magnetic particles and to mesure the force generated by this confined polimerization in vitro and in vivo), nucleus rheology (the ability of dendritic cell to internalize the magnetic particles will allow mesurement directly on the nucleus) and force measurements during migration in confined channel (by combining the micro-fabrication technics of the PMMH and the microfluidic technology at Institut Curie we hope to design microchannels with variable rigidity or magnetic parts to be able). The modelization of these phenomena will be realized in collaboration with Raphaël Voituriez (Laboratoire Jean Perrin, UPMC). Modeling will be done for each set of experiments.
Name : UMR 7636
Director : Philippe PETITJEANS
Supervisor(s) : Olivia DU ROURE
Team leader : Olivia DU ROURE
Funding : ITMO Cancer
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