Biophysical Society Thematic Meeting| Aussois 2019

Biology and Physics Confront Cell-Cell Adhesion

Poster Abstracts

24-POS Board 24 TRUSS-LIKE ARRANGEMENT OF CADHERINS IS RESPONSIBLE FOR DESMOSOME STRENGTH Mateusz Sikora ; Anna Seybold 2 ; Max Linke 1 ; Gerhard Hummer 1 ; Achilleas Frangakis 2 ; 1 Max Planck Institute of Biophysics, Frankfurt am Main, Germany 2 Goethe University, Frankfurt am Main, Germany Desmosomes are long-lasting cell-cell junctions that endow mature tissues with mechanical stability. The core of the desmosomal adhesion is formed by cadherins, specialised calcium- dependent transmembrane proteins. Together with other adaptor proteins, the cadherins connect cortices of neighbouring cells. Robustness to external stress comes from a particularly dense arrangement of cadherins, which form characteristic electron-dense structures visible in EM micrographs. However, the structural details of desmosomal cadherin assemblies remain controversial despite their relevance for various diseases. To address and resolve these controversies, we performed large-scale molecular dynamics simulations of a different 3D cadherin arrangements in the desmosome. We found that only an antiparallel, truss-like arrangement of cadherins can explain both the mechanical robustness and the spacing observed between plasma membranes in the desmosome. We validated our predictions by cryo-electron tomography of the desmosomes from mouse liver.

63