Project

Back to overview

Active patterned surfaces and morphogenesis of biological tissues

Applicant Salbreux Guillaume
Number 197068
Funding scheme Project funding (Div. I-III)
Research institution Département de Génétique et Evolution Faculté des Sciences Université de Genève
Institution of higher education University of Geneva - GE
Main discipline Theoretical Physics
Start/End 01.09.2021 - 31.08.2025
Approved amount 612'081.00
Show all

All Disciplines (3)

Discipline
Theoretical Physics
Embryology, Developmental Biology
Biophysics

Keywords (9)

non-equilibrium physics; cell differentiation; embryonic development; active matter; pattern formation; self-organization; physics of living matter; morphogenesis; collective phenomena

Lay Summary (French)

Lead
Les organismes biologiques se développent à partir d’une seule cellule embryonnaire. Pour établir des structures complexes ils doivent être capables de s’auto-organiser. Cela est possible grâce au couplage étroit entre les réseaux de signalisation cellulaire qui permettent aux cellules de communiquer, et à la génération de force qui leur permet de se déformer. Le but de ce projet est d’explorer, en utilisant des outils de physique théorique, comment ces deux aspects permettent aux tissus biologiques de s'auto-organiser.
Lay summary

Contenu et objectifs du travail de recherche

Nous étudierons l'auto-organisation des tissus épithéliaux en décrivant un tissu biologique comme une surface de fluide actif, c'est à dire maintenue hors d’équilibre par une source d’énergie chimique. Nous explorerons d’abord de facon générale les déformations physiques qui peuvent survenir dans un tel tissu quand les cellules ont une polarité, c’est-à-dire un axe préférentiel, et adoptent different types cellulaires. Nous étudierons ensuite comment le couplage entre mécanique et signalisation permet une morphogenèse précise lors de la formation des veines dans l'aile de Drosophile. Nous établirons un modèle des principaux réseaux de signalisation impliqués dans la décision d’une cellule de former une veine. Nous étudierons comment cette interaction assure la robustesse dans la localisation et la forme du motif des veines.

Contexte scientifique et social du projet de recherche

Le projet relève de la recherche fondamentale. Les résultats permettront de mieux comprendre la façon dont des cellules biologiques parviennent à former un tissu et plus généralement un organe, ce qui sur le long-terme pourrait amener à des applications médicales.

Direct link to Lay Summary Last update: 28.10.2020

Responsible applicant and co-applicants

Employees

Project partner

Abstract

Biological organisms can establish a complex body plan from a single cell embryo, producing patterns and three-dimensional structures at the tissue scale with remarkable precision. Biological self-organization is inherently mechano-chemical, and rely on a tight coupling between gene regulation, signalling networks, and cellular force generation. The general principles by which the interplay of tissue mechanics and cell-cell communication allow for robust morphogenesis are however not understood. The framework of active matter, describing collective ensembles of physical objects driven out-of-equilibrium at the microscopic level, is well suited to provide a quantitative description of biological systems. In this proposal, we will investigate self-organization of epithelial tissues by describing a biological tissue as an active fluid nematic or polar surface, with coexisting domains representing different cell states. We will explore how this coarse-grained, minimal description recapitulate morphogenesis observed {\it in vivo} and during growth of {\it in vitro} organoids. We will carry out this research along two main objectives. In objective 1, we will explore physical deformations arising in a nematic or polar active fluid sphere, subjected to internal active bending moments. Active bending moments arise in a tissue from the distribution of stresses along the apico-basal polarity axis. In addition, morphogen dynamics and cell fate specification on the surface will be captured with a low-dimensional phenomenological dynamics, following the idea of Waddington's landscape. Using linear stability analysis and finite element simulations, we will explore the shape changes that such an active surface can achieve, as a function of a few key parameters. In objective 2, we will study how coupling between mechanics and signalling enables precise morphogenesis during vein formation in the {\it Drosophila} wing. We will represent key signalling networks involved in cell fate specification by phenomenological variables, which move with the tissue flow and control cellular mechanical stresses. We will study how this interplay ensures robustness in the localisation and shape of the pattern. This project will unravel the fundamental principles by which biological tissues self-organize, as well as establish engineering principles that can be used to design self-organizing active matter.
-