Design and mechanical characterization of mechanofluorescent prototissues

The Doctoral School of the University of Montpellier offers several PhD grants to carry on a PhD in Physics in the Laboratory Charles Coulomb (L2C), starting on October 2023 and for a duration of three years.

In the context of this call Drs. Laura Casanellas and Remi Merindol, from the Soft Matter team at L2C, offer the possibility of cosupervising a PhD Thesis on the ¨Design and mechanical characterization of mechanofluorescent prototissues¨.

The period for online applications will start on April 2023 and an audition will take place on early May 2023 for the final selection of candidates.

Scientific Project :

The behaviour of biological tissues under mechanical stress controls many processes from organ development during embryogenesis to tumour growth and spreading. Yet it is challenging to determine the key parameters that govern their mechanics using biological tissues because of their complexity and due to the lack of tools to visualize stress distribution in situ. Synthesizing model materials that mimic biological tissues and allow visualizing inhomogeneous stress distribution is thus necessary to rationalize tissue mechanics.

This project aims to create mechanofluorescent biomimetic prototissues that change fluorescence under stress in order to visualize and quantify stress inhomogeneity under loading. In the Soft Matter team, we already optimized key techniques for this project. L. Casanellas developed the assemblies of biomimetic tissues from Giant Unilamelar Vesicles (GUVs) [1] and R. Merindol developed the use of mechanofluorescent DNA force probes containing FRET pairs (Froster Resonance Energy Transfer) to visualize stress [2].

The PhD project is organized around three main objectives:

First, the controlled assembly of prototissues using DNA. A key feature will be the incorporation of FRET based DNA probes that become fluorescent under stress. Playing on the length, geometry and areal density of DNA strands will allow us to tune the adhesion between GUVs. We also plan to incorporate all-DNA microgels inside the GUVs in order to mimic the cell cytoskeleton [3]. This section will provide tuneable self-reporting building blocks for the design of prototissues.

Second, we will implement the assembly of GUV in microfluidic chips to control the shape and composition of the prototissues. It will also allow us to prepare more complex tissues by mixing multiple building blocks displaying different features (in adhesiveness, mechanofluorescence, or presence of cytoskeleton). This section will provide us with reproducible prototissues samples that mimic biological ones.

Third, we will quantify the mechanical behaviour of these prototissues [4]. We will use a nano-indenter designed for soft materials coupled to a confocal microscope to characterize the mechanical properties of the individual GUVs building blocks and biomimetic prototissues. We will map stress during indentation by imaging the mechanofluorescent DNA probe using confocal fluorescence microscopy. This section will identify and quantify the relation between building block features and their mechanical response in tissues.

Recent publications related to the topic :

[1] Casas-Ferrer, L., Brisson, A., Massiera, G. & Casanellas, L. Design of vesicle prototissues as a model for cellular tissues. Soft Matter 17, 5061–5072 (2021).

[2] Merindol, R., Delechiave, G., Heinen, L., Catalani, L. H. & Walther, A. Modular Design of Programmable Mechanofluorescent DNA Hydrogels. Nat. Commun. 10, 528 (2019).

[3] Merindol, R.; Loescher, S.; Samanta, A.; Walther, A. Pathway-Controlled Formation of Mesostructured All-DNA Colloids and Superstructures. Nat. Nanotechnol. 13, 730–738 (2018).

[4] M. Layachi, L. Casas-Ferrer, G. Massiera, L. Casanellas, Rheology of vesicle prototissues : a microfluidic approach. Front. Phys. 10:1045502. DOI: 10.3389/fphy.2022.1045502

The Laboratoire Charles Coulomb (L2C, UMR 5221 CNRS and Université Montpellier, UM) is a plurithematic physics laboratory based in the Montpellier Triolet Campus. The soft matter group is composed of 17 permanent researchers and about 6 PhD students and postdocs. In addition to fully equipped chemistry rooms for sample preparation and basic characterization, a wide palette of techniques and setups are available and readily accessible to all team members: (confocal) microscopy, rheology, AFM, static and dynamic light scattering, small angle X-ray scattering…

Several collaborative projects, regular group seminars and a lively and friendly atmosphere make the experience of students and postdocs at L2C enjoyable and profitable.

We are looking for a highly motivated candidate to join our team, willing to carry on experimental research in a multi-disciplinary topic. The PhD candidates should have a Master’s or comparable degree in biophysics, physics, chemistry, or in a related subject. Knowledge of experimental techniques (microscopy or microfluidics), image processing and data analysis will be appreciated. A good level in both written and spoken English is required.