PhD

Title: Force nanosensor development for measuring mechanical stress exerted by living cells

Project summary

Membrane adhesion receptors and cytoskeleton are two key elements in cell biology mechanotransduction. The molecular machinery of mechanotransduction is a transversal hot topic that gives rise to intense activity in scientific theme mixing physics, chemistry, biochemistry and biology. Our ability to understand mechanical cues in biology is limited by our capability to measure it in living cells. Therefore, the spatio-temporal dynamics and regulation of active zones involved in mechanosensing, typically at focal adhesion sites, are still poorly understood. This collaborative project proposes to develop a new Force NanoSensor (FNS) allowing to measure and map the mechanical strains exerted by living cell. This probe is composed of an extendible elastic molecule, flanked by two emitters at its ends, including a quantum dot or a nanoplatelet. The force measurement will be achieved when the elastic molecule is stretched, and Förster Resonant Energy Transfer (FRET) will constitute the way to quantify this stretching at the nanoscale. In this project we also propose to highlight the benefits of our new force nanosensor to probe mechanosensing processes by developing two original applications. These applications will require to implement FNS probes for super-resolution fluorescence imaging. The first application will use a biomimetic platform allowing to investigate the dynamics of cytoskeleton contractility on integrin focal adhesion complex. The second application will consist in measuring the dynamic of contractile forces in 2D and 3D environment, generated by fibroblasts.

Preferred skills and application

This interdisciplinary PhD project will mobilise plenty of experimental techniques from quantum dots synthesis and their biofunctionnalization, to single molecule techniques including fluorescence imaging (FRET) and force spectroscopy (optical tweezers, microfluidic). Living cells preparation and manipulation will be also involved, as well as surface chemistry. Thus, we are seeking a highly motivated, inquisitive candidate, eager to work in an interdisciplinary environment to realise a PhD at the interface between cell biology, biophysics and optics. The candidate may have an initial background in biology, physics, biophysics or chemistry, with a strong aptitude for experimental work.

The PhD support is fully funded from an ANR project. For more details about the project and to apply, please send a motivation letter, a CV, your Master grades to Rodolphe Jaffiol (rodolphe.jaffiol@utt.fr). Additional recommendation letters will be highly appreciated. The PhD project is supposed to start in summer or late 2024.