ESPCI web site
ESPCI PARIS
Lieu de travail :
Paris - Ile-de-France - France
Intitulé du sujet :
Growth and mechanics of actin filament networks
Champs scientifiques :
– Biologie
Description
Actin is a major component of biological cells and forms filaments that constantly polymerize and depolymerize. This activity is used by the cell to generate forces in order to crawl on a surface during developmental migration, wound healing or cancer metastasis or to pinch part of its membrane during endocytosis. The filaments are arranged in different structures than can be very dense networks like the cortex below the plasma membrane. The cortex endows its viscoelastic properties to the cell and protects it from unwanted deformations. Neither the actin force generation by the transduction of biochemical energy to mechanical work nor the viscoelastic properties of these filaments networks are at present fully understood from a biophysical point of view.
To delve into these problems, reconstitution of active dense actin networks has to be performed at the microscopic scale. We recently developed a new method using strings of self-organized cylindrical micro-magnets to probe the viscoelastic properties of actin networks as well as the force generation during their assembly (Bauër et al Scientific Reports 2017). Reconstituted actin networks grow from the faces of the cylinders and an attractive force between adjoining magnets is applied to hamper the growth or to probe the viscoelastic properties of the network. Compared to other techniques, this technique takes advantage of the self-organization of the cylinders to achieve at least an order of magnitude more experiments than other technique like AFM.
This PhD project aim is to tackle two specific questions :
1) In the cell, there is a constant de-polymerization of the filaments and recycling of the actin network that are monitored by a host of regulatory proteins. By using these regulators in vitro, we can tune the level of disassembly in the network which is expected to have a profound effect on its viscoelastic behavior. In this context we aim at identifying the conditions in which the cell is able to generate a force by polymerization when the network on which it rests is itself viscously flowing. This part of the project will benefit from our ongoing collaboration with specialists of single actin filaments biochemistry G Romet Lemonne and A. Jégou lab in Institut Jacques Monod.
2) We have previously evidenced a peculiar mechanical property of the actin networks grown under negligible force : the stress required to deform a network grows exponentially with the deformation. This can be explained theoretically for poorly connected networks at the isostatic limit. We are currently working with the lab of Martin Lenz in LPTMS Orsay to develop numerical models of such networks. We want to test these models with networks grown at different forces or with a different density of connections in order to better understand this nonlinear mechanics of actin filament networks and how the cell can harness these properties to adapt its deformation to external load.
Overall, this project will use an original, cutting edge biophysical technique to answer crucial questions on cell motility and mechanics.
3i aspect of the project
This project stands at the frontier between Biology and Physics. From the biological point of view it is crucial to understand the mechanisms allowing the cell to generate forces to achieve many cellular processes essential to life. From the physics point of view, actin networks is a unique example of rigid or semi-flexible polymer gels whose mechanical properties are far from being fully understood. Although this project treats with fundamental questions, cell mechanics and mobility is of prime importance for future research in pharmaceutical applications, specifically in cancer treatment. In an engineering perspective, the nano/microtechnology techniques that will be used and developed in this project are of critical value in modern high-tech industries. This project will benefit from the different well-established collaborations of the team with internationally recognized teams including Yale University with which we’re exchanging students.
Nature du financement :
Financement public/privé
Précisions sur le financement
MSCA Cofund UPtoPARIS
Présentation établissement et labo d’accueil
ESPCI PARIS
UMR7636 Physics & Mechanics of Heterogeneous Media
The PMMH is a multidisciplinary research laboratory dedicated to hydrodynamics, solid mechanics and granular materials, including several soft matter and biophysics themes at the interface with biology and chemistry. It belongs to ESPCI Paris (and thus to PSL Research University) and is also affiliated to CNRS (UMR 7636) and to Sorbonne Univesité (formerly UPMC) and Université Sorbonne Paris Cité (through Université Paris Diderot). The team Cell Biophysics develops new experiments to elucidate the biophysical processes at play in cell mechanics and motility. The general framework is to fabricate and use superparamagnetic colloids, cylinders and micro-patterns to exert and measure forces on micro-objects. Dipolar attraction between two magnetic structures develops nanoNewton forces which are relevant for biology. Self-organization properties of the magnetic micro-objects is a key to carry out systematic experiments. The main focus is the actin cytoskeleton in vitro but the approach has been recently extended to in-cellulo studies.
https://www.pmmh.espci.fr/?Cell-Biophysics
Name of the supervisor
OLivia Du Roure
Name of the co supervisor
Julien Heuvingh
Site web :
https://www.upto.paris/
Profil du candidat
We attempt to recruit a highly motivated PhD student with an appetite for interdisciplinary work and laboratory experiments in a project that will involve discussing with physicists, biologists, engineers and technical staff in different sites. The ideal candidate should have a degree in Physics, Biophysics or Biology. Physicist candidates should have a strong interest in biological questions whereas biologist candidates are expected to have been trained at least one course of physics or biophysics and to have a strong motivation to work in a physics. Experimental skills biochemistry, microfluidics and/or microfabrication will be appreciated but are not required.
Date limite de candidature
17/09/2018
> 25 et < 35 K€ brut annuel
Applications must be submitted on the UPtoPARIS website : https://www.upto.paris/
More information is available in the "How to apply" section of the website