Description du projet
Modéliser les forces générées par les cellules qui restructurent leur micro-environnement
Les cellules sentent et s’adaptent constamment aux signaux de leur micro-environnement. En plus des signaux biochimiques, elles répondent aux signaux mécaniques ou biophysiques et peuvent également en envoyer. Ces mécanismes sont mal compris. De récentes recherches ont révélé que les forces générées par les cellules permettent de restructurer leur substrat sous-jacent. Avec le soutien du programme Actions Marie Skłodowska-Curie, le projet TopCellComm développera un cadre de calcul pour modéliser ces forces. Combinant le formalisme du champ de phase et un modèle mathématique de déformation non linéaire du substrat, le cadre apportera un éclairage sur les mécanismes sous-jacents aux interactions des cellules uniques et des paires de cellules avec les substrats sous-jacents. L’objectif ultime consiste à développer un outil prédictif pour soutenir la conception de biomatériaux destinés à la médecine régénérative.
Objectif
The processes through which cells sense, adapt, and respond to their environment are fundamental to development and homeostasis. Mechanical forces, exerted and experienced by cells, can act as messengers, however, the exact mechanisms by which cells perceive and generate forces have not been elucidated yet. Here, I aim to explore a phenomenon, in which cells autonomously exploit folding and topographical restructuring of their underlying substrates as a means of self-induced guidance and communication mechanism to coordinate their individual and collective behaviours. Guided by the Prof. Doostmohammadi group’s recent collaborative study, revealing cell-generated forces from the folding patterns in real-time, I will develop a computational framework and will use it to numerically dissect the crosstalk between cell activity and self-generated patterns of substrate deformation. To model cell-generated forces, I will employ the phase-field formalism coupled will be coupled to the mathematical model of nonlinear substrate deformation. By utilising available data, I will calibrate the model and carry out simulations to uncover the underlying mechanics of single cell interactions with the substrate and emergent topographic anisotropies. I will then extend the model to consider interaction between pairs of cells on a substrate and elucidate the phenomena of topography-mediated cell communication. These actions will act as a first step towards the interconnection between multicellular-scale self-organized topographic modification and cell migration. Thus, this project at the intersection of mathematics, biology, and bioengineering will be a significant step towards delivering a state-of-the-art predictive tool for the design of biomaterials for regenerative medicine.
Champ scientifique
Programme(s)
- HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA) Main Programme
Régime de financement
MSCA-PF - MSCA-PFCoordinateur
1165 Kobenhavn
Danemark