Biophysical Society Thematic Meeting| Aussois 2019

Biology and Physics Confront Cell-Cell Adhesion

Wednesday Speaker Abstracts

KINETIC NUCLEATION-DEPENDENT E-CADHERIN CLUSTERING REGULATES ALPHA-CATENIN CONFORMATIONAL ACTIVATION Kabir H. Biswas 1 ; 1 Hamad Bin Khalifa University, College of Health & Life Sciences, Doha, Qatar E-cadherin-based cell-cell adhesion (E-cadherin adhesion) is essential for organogenesis and maintenance of the epithelial tissue, and a loss of cell-cell adhesion has been suggested to contribute to cancer development. In addition to performing its adhesive function through the extracellular domain-mediated homotypic interaction, E-cadherin adhesion enables cells to sense mechanical tension in the tissue through the adaptor protein, alpha-catenin. This has been proposed to be mediated through, in part, a conformational change in alpha-catenin upon increase in the actomyosin tension on E-cadherin adhesion resulting in the availability of cryptic binding sites in alpha-catenin leading to an enhancement in its interaction with vinculin, an adaptor protein that is homologous to alpha-catenin, and the actin cytoskeleton. Reconstitution of E-cadherin adhesion in a hybrid format wherein a live cell interacts with a synthetic, supported lipid bilayer functionalized with the extracellular domain of E-cadherin showed that cells utilize filopodia to cluster E-cadherin. Importantly, E-cadherin clustering requires a reduced diffusive mobility of the protein on the membrane indicating the presence of a step of kinetic nucleation in the process. Further, experiments with nanopatterned supported lipid bilayer substrates revealed that the size of E-cadherin clusters regulate the conformational activation of alpha-catenin. Once activated, however, alpha-catenin is sustained in the active conformation even when actomyosin tension in the cell is reduced pharmacologically. Thus, membrane diffusion-regulated E-cadherin clustering impacts alpha-catenin conformational activation and mechanical signaling.

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