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

Andrew J. Price, Anna-Lena Cost, Hanna Ungewiß, Jens Waschke, Alexander R. Dunn () and Carsten Grashoff ()
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Andrew J. Price: Stanford University
Anna-Lena Cost: Max Planck Institute of Biochemistry
Hanna Ungewiß: LMU Munich
Jens Waschke: LMU Munich
Alexander R. Dunn: Stanford University
Carsten Grashoff: Max Planck Institute of Biochemistry

Nature Communications, 2018, vol. 9, issue 1, 1-11

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

Date: 2018
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DOI: 10.1038/s41467-018-07523-0

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