UBC Math Bio Seminar: Vijay Rajagopal

  • Date: 11/30/2022
  • Time: 14:00
Lecturer(s):
Vijay Rajagopal, University of Melbourne
Location: 

University of British Columbia

Topic: 

Mechanistic modelling studies of the mechanobiology of cell-cell adhesions

Description: 

Adherens junctions (AJs) are protein complexes at the cell-cell interface that withstand mechanical forces and maintain tissue structure. They also regulate intracellular signalling for cell growth, division and death. Proper adherens junction structure and function is therefore critical for tissue development. Adherens junction dysfunction causes cancer metastasis. AJs involve extracellular bindings between cadherin molecules and intracellular interactions between cadherins and the actin cytoskeleton. Both cadherin and actomyosin cytoskeletal dynamics are reciprocally regulated by mechanical and chemical signals, which subsequently determine the strength of cell-cell adhesions and the emergent organization and stiffness of the tissues they form. We present a new mechanistic computational model of intercellular junction maturation in a cell doublet to investigate the mechano-chemical crosstalk that regulates AJ formation and homeostasis. The model couples a 2D lattice-based model of cadherin dynamics with a continuum, reaction diffusion model of the reorganizing actomyosin network through its regulation by Rho signaling at the intercellular junction. We demonstrate that local immobilization of cadherin induces cluster formation in a cis less dependent manner. We then recapitulate the process of cell-cell contact formation. Our model suggests that cortical tension applied on the contact rim can explain the ring distribution of cadherin and F-actin on the cell-cell contact of the cell-doublet. Furthermore, we propose and test the hypothesis that cadherin and F-actin interact like a positive feedback loop, which is necessary for formation of the ring structure. Different patterns of cadherin distribution were observed as an emergent property of disturbances of this positive feedback loop.

Other Information: 

Location: Online. Contact Katie Faulkner for link.

 

Time: 2pm Pacific