Mechanical loading of desmosomes depends on the magnitude and orientation of external stress

• DOI: 10.1038/s41467-018-07523-0
• Publication Date: 2018-12-05T12:55:47Z
• Authors: Andrew J. Price; Anna-Lena Cost; Hanna Ungewiß; Jens Waschke; Alexander R. Dunn; Carsten Grashoff
• Keywords: Desmoplakin; Desmosome

Desmosomes are intercellular adhesion complexes that connect the intermediate filament cytoskeletons of neighboring cells, and essential for mechanical integrity mammalian tissues. Mutations in desmosomal proteins cause severe human pathologies including epithelial blistering heart muscle dysfunction. However, direct evidence their load-bearing nature is lacking. Here we develop Förster resonance energy transfer (FRET)-based tension sensors to measure forces experienced by desmoplakin, an obligate protein links plaque filaments. Our experiments reveal desmoplakin does not experience significant under most conditions, but instead becomes mechanically loaded when cells exposed external stresses. Stress-induced loading transient sensitive magnitude orientation applied tissue deformation, consistent with a stress absorbing function desmosomes distinct from previously analyzed cell complexes.