Project description
Modelling cell-generated forces restructuring their microenvironments
Cells constantly sense and adapt to signals in their microenvironment. In addition to biochemical signals, cells respond to mechanical or biophysical signals and can also send them. The mechanisms are poorly understood. Recent research has revealed cell-generated forces to be able to restructure a cell’s underlying substrate. With the support of the Marie Skłodowska-Curie Actions programme, the TopCellComm project will develop a computational framework to model these forces. Combining phase-field formalism with a mathematical model of nonlinear substrate deformation, the framework will shed light on the mechanisms underlying interactions of single cells and cell pairs with the underling substrates. The ultimate goal is a predictive tool to support biomaterial design for regenerative medicine.
Objective
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.
Fields of science
Programme(s)
- HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA) Main Programme
Funding Scheme
MSCA-PF - MSCA-PFCoordinator
1165 Kobenhavn
Denmark