DS10 - Défi des autres savoirs

A Biomimetic Approach to Tissue Mechanics – BOAT

Submission summary

In this project, we propose to study novel tissue-mimetic systems to understand the physical basis of collective remodeling in biological tissues. In particular, we will study how the interplay between adhesion and forces controls the emergence of tissue architecture during morphogenesis. Indeed, during morphogenesis the homogeneous cell aggregate is subjected to large movements that give rise to the highly organized 3D structures found in the embryo. Using a bottom-up approach will allow us to identify the minimal ingredients necessary to reproduce such collective processes by isolating the passive mechanical pathways of self-assembly in adhesive synthetic tissues.

In particular, we will transpose this biological problem into a soft matter framework and will use biomimetic emulsions that were shown to reproduce the minimal mechanical and adhesive properties of cells in biological tissues. These emulsions are stabilized with a monolayer of phospholipids that reproduce the fluidity of the cell membrane, and can be functionalized with adhesive proteins to mimic cell-cell adhesion in tissues. Moreover, index matching of the oil and water phases makes the emulsions transparent. This allows us to image their microstructure in 3D, to measure the strength of the adhesion between droplet pairs and to quantify the propagation of forces within the packing through the analysis of droplet shapes.

We will study the mechanical behavior of these emulsions under various types of mechanical perturbations. First we will introduce those perturbations locally through the insertion of deformable particles in the 3D packing. Indeed, in tissues, the individual cells can exert forces on cell-cell contacts by exchanging neighbors or changing their shape, thus injecting energy locally. We will design the particles so that they will apply mechanical perturbations with controllable amplitudes and frequencies in the bulk of the emulsion. Second, we will study the mechanical behavior of the emulsion when the perturbation is applied externally. To this end we will impose a global compression of the emulsions by flowing them in microfluidic constrictions with controlled geometries.

In both cases, image analysis will allow us to distinguish between two types of behavior in the emulsion: (1) the droplets can keep their respective positions in the packing and only be elastically deformed by the perturbation, thus leading to the development of force bearing chains in the packing; (2) the droplets can adapt to the perturbation by rearranging positions with their neighbors, thus exhibiting an irreversible plastic response. In this case, some adhesion patches will be disrupted while new adhesions will have to be created de novo. The dynamical response of this emulsion, in which specific binders ensure adhesion, should thus deeply differ from the one of repulsive emulsions or even from the one of emulsions where attraction is mediated through non-specific depletion attraction.

We will use the results obtained from this biomimetic approach in order to map out a phase diagram describing the underlying elasto-plastic mechanisms governing remodeling in biological tissues. In particular, for a given adhesion level and for given mechanical properties, we will be able to predict the dominant mechanism for tissue deformation. We will further test our results by comparing them with similar experiments carried out on cellular aggregates, which constitute a biological model system for tissues in vivo. Those findings will reveal the underlying regulations of adhesion and mechanical properties that take place in cells during the remodeling of tissues, and will more generally shed light on the physical processes at stake during embryonic development.

Project coordination

Léa-Laetitia PONTANI (Laboratoire Jean Perrin)

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.

Partner

LJP Laboratoire Jean Perrin

Help of the ANR 306,015 euros
Beginning and duration of the scientific project: January 2018 - 48 Months

Useful links

Explorez notre base de projets financés

 

 

ANR makes available its datasets on funded projects, click here to find more.

Sign up for the latest news:
Subscribe to our newsletter