Dynamic and multiscale processes of auto-organisation in tissue morphogenesis

Summary:

(please also visit our team webpage here: https://sites.google.com/view/paotim/accueil)

Recent advances in mechanobiology and microtechnology have synergistically converged into the development of biomimetic systems improving in vitro culture models, called organ-on-chips. In such microphysiological systems, cells can benefit from the integration of crucial physiological cues thanks to engineering, allowing to achieve a prolonged preservation of the primary functional phenotypes of the cells, normally hindered in vitro.

In order to design more appropriate biological architectures restoring native conditions with high fidelity, we aim at studying and identifying the impact on cells and tissues of critical key parameters such as mechanics, geometry, dynamics and soluble morphogen/biochemical gradients. In particular, we are interested in studying and recapitulating physico-chemical cues orchestrating self-organization processes responsible for the natural architectures found in organs Assuming that these structures are promoting the phenotypes desired in vitro, we hypothesize that our approach could help us rescue physiological or pathological tissue architectures and examine these processes dynamically in vitro.

Our team currently focuses on the development of a liver-sinusoid-on-a-chip as a model: as the multicellular functional unit of the liver, it is the core of complex and poorly understood processes occurring in a variety of pathologies closely linked to mechanical stimuli and leading to fibrosis, cirrhosis or cancer. We hope that our team can contribute to a global effort aiming at responding to the current urgent needs for high-fidelity models enabling the study of these processes towards a better comprehension of the diseases and maybe future therapeutic solutions.

In this endeavor, the team develops multi-layered microfluidic platforms integrating mechanical control of substrate stiffness, luminal pressure and shear stress for multicellular culture. Thanks to our collaborations, we constantly work on the improvement of physico-chemical cues present inside the study-devices to let the cells freely shape their morphofunctional tissues. We are thus interested in physical models of morphogenesis as a response of cells to their direct microenvironment.

The team started officially at LBD-IBPS (UMR7622) on September 1st 2021 and is developing thanks to the help of close collaborators and to funding support, detailed below.

We will share news and results when available.

Collaborations

National collaborations:- Marc-Antoine Fardin, Institut Jacques Monod, CNRS, Team Cell Adhesion and Mechanics (Ladoux-Mège team), Institut Jacques Monod, CNRS, Paris, France
- Karine Clément and NutriOMICS Team (Chloé Amouyal and Simon Lecoutre and collaborators), Sorbonne Université and INSERM, Hôpital La Pitié Salpêtrière, Paris, France (3 funded projects)
- Isabelle Cremer and Catherine Monnot, Centre de Recherche des Cordeliers, Sorbonne Université, Université de Paris, INSERM, Paris, France (3 funded projects)
- Stéphanie Graff-Dubois, Sorbonne Université, Hôpital La Pitié Salpêtrière, Paris, France (1 funded project)
- Pierre-Emmanuel Rautou, Centre de Recherche sur l’Inflammation, INSERM, Université de Paris, UMR1149, Clichy, France.
International collaborations:
- LaNSBioDyT, Facultad de Ciencias, UNAM, Mexico (teams: Tatiana Fiordelisio-Coll; Marina Macias-Silva; Genaro Vázquez-Victorio)

Additional information

https://sites.google.com/view/paotim/accueil

  • micropatterning and microstructuring