Biophysical Society Thematic Meeting| Aussois 2019

Biology and Physics Confront Cell-Cell Adhesion

Monday Speaker Abstracts

A COMPUTATIONAL MODEL COUPLING E-CADHERIN DYNAMICS AND ACTOMYOSIN NETWORK ILLUSTRATES THE CELL-CELL CONTACT MATURATION Qilin Yu 1 ; Rodney Luwor 2,3 ; William Holmes 4 ; Vijay Rajagopal 1 ; 1 University of Melbourne, Department of Biomedical Engineering, Parkville, Australia 2 University of Melbourne, Department of Surgery (RMH), Parkville, Australia 3 University of Melbourne, Department of Microbiology & Immunology, Parkville, Australia 4 Vanderbilt University, Department of Physics and Astronomy, Nashville, TN, USA E-cadherin based intercellular adhesion plays a fundamental role in many biological processes including tissue development, wound healing, tissue integrity and cancer metastasis. Previous studies have demonstrated that cell-cell contact formation is regulated by a variety of biochemical pathways that modulate the actomyosin cytoskeleton and the cadherin-catenin- complex – two key players in the intercellular junction formation. Furthermore, micropipette- based cell-cell doublet experiments have shown that mechanical forces experienced by the cells also play an important role in the formation of the intercellular junction. However, a quantitative understanding of the complex interplay between these mechanical forces and the biochemical pathways remains to be resolved. In this study, we present a new computational model of intercellular junction maturation in a cell doublet. The model couples a 2D lattice-based model of E-cadherin dynamics with a continuum, reaction-diffusion model of the reorganizing actomyosin network and it’s regulation by Rho signaling at the intercellular junction. In the model, the force balance around the cell-cell contact evolves as a result of interactions between E-cadherins and the actomyosin network. These forces feedback to the intercellular junction through force sensitive molecules, such as myosin and α-catenin. The model can recapitulate the asymmetric distribution of E-cadherins and related molecules on the rim of the cell doublet contact due to the asymmetric forces along the contact. These results demonstrate how the interplay between mechanical forces and chemical signaling lead to changes during the contact maturation.

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