PHD2018-13

Deciphering the interplay between cell polarity and inter-cellular forces in epithelial 3D organization

Host laboratory and collaborators

Elsa Bazellières / IBDM / elsa.bazellieres@univ-amu.fr

Matthias Merkel / CPT / matthias.merkel@posteo.de

Scientific background

Epithelial tissues are 3D cell sheets that display a high degree of organization, including cell polarity (reflected in an asymmetric localization of polarity proteins), characteristic cell shapes, and a layered structure. However, this organization is lost during cancer progression, when cells start to migrate. How exactly epithelial organization is controlled has remained elusive, but biophysical studies point towards complex interactions between chemical, genetic, and mechanical signals like inter-cellular forces. Within this project, we will study how epithelia with different genetic backgrounds adapt their organization and forces in response to their mechanical environment.

PhD Objectives

We want to (i) use hydrogel beads to investigate the mechanisms that couple cellular force generation to the localization of polarity proteins, and (ii) study how these mechanisms depend on the cellular microenvironment in 3D cell aggregates.

Proposed approach

Deformable hydrogel beads will be used as force reporters, which will be encapsulated in 3D wildtype or mutant aggregates. Bead coating (different cadherins or integrins) and bead rigidity will be tuned to mimic the overall adhesion and mechanics of the surrounding cells, where bead rigidity can be gauged using atomic force microscopy (AFM). Actin dynamics and bead deformation will be imaged on a spinning disk microscope. From the bead deformation, cellular forces will be extracted by refining existing computational inversion methods.

PhD student’s expected profile

We are looking for a PhD student with a strong interest in collaborative and interdisciplinary research. Ideally, he/she should have some basic experimental skills (cell culture, imaging). Moreover, even though programming skills or experience in mathematical work are not a must, they are a clear advantage. An interest in dealing with theoretical concepts is expected. The candidate will be given the opportunity to learn state-of-the-art experimental techniques (CRISPR/Cas9, optogenetics, microgels, AFM), image analysis techniques (image processing, mathematical representation of objects), computational methods (conjugate gradient minimization), and physical concepts (tensors, elasticity theory, spherical harmonics). The student will thus not only learn the full know-how required to achieve the project, but also acquire a versatile and solid toolset that will be useful for any kind of inter-disciplinary biophysical research.

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