Hamid Jafarinia


Project description:

Integrin-based mechanotransduction enables cells to sense and respond to changes in their environment. YAP is a crucial downstream player of integrin-based signaling whose function depends on translocation from the cytoplasm to the nucleus. The phosphorylation of YAP regulates its ability to enter the nucleus. Recent findings show that YAP can be recruited to adhesions to be directly phosphorylated. It is however not clear how properties of integrin adhesions, such as changes in cluster size and distribution due to stiffness or extracellular matrix composition, can affect this process. To address this, we are developing a spatial particle-based model to study how YAP phosphorylation through direct binding to integrin adhesions is regulated by the adhesion properties. In our model, integrin adhesions are randomly fixed on a membrane at the bottom of the simulation box, and inactive YAP molecules are initialized randomly in the simulation box with a diffusion rate. Our model takes into account the association and dissociation of YAP with the adhesions and phosphorylation (in the adhesion) and dephosphorylation (in the cytoplasm) of YAP. In summary, the aim of this project is to gain more knowledge on the mechanisms by which cells sense and adapt to their environments, which can aid in developing improved cancer and regenerative medicine treatments.

Keywords: Mechanotransduction, YAP/TAZ phosphorylation, spatial stochastic model
Techniques: Computational modeling using a Monte Carlo algorithm