Actomyosin forces trigger a conformational change in desmoplakin within desmosomes
Yinchen Dong1, Ahmed Elgerbi2, Bin Xie3
1Department of Biomedical Engineering, University of California, Davis, CA, USA.
Nature Communications
|October 10, 2025
Summary
Desmosomes sense mechanical forces via desmoplakin, a key protein. Actomyosin forces alter desmoplakin
Area of Science:
- Cell biology
- Biophysics
- Structural biology
Background:
- Desmosomes are crucial for mechanical stress resistance in tissues like skin and heart.
- Desmosomal dysfunction is linked to skin disorders, cardiomyopathies, and cancer.
- The mechanism by which desmosomes sense and respond to mechanical forces remains unclear.
Purpose of the Study:
- To investigate how desmosomes sense and respond to mechanical stimuli.
- To elucidate the role of actomyosin forces in desmosome mechanics.
- To determine if desmoplakin is mechanosensitive.
Main Methods:
- Super-resolution imaging in epithelial cells and cardiomyocytes.
- Förster resonance energy transfer (FRET)-based tension sensors.
- Atomistic computer simulations and biochemical assays.
Main Results:
- Actomyosin forces induce a conformational change in desmoplakin, a key desmosomal protein.
- Keratin-19 links F-actin to desmosomes in MCF7 cells, regulating force integration.
- Actomyosin contractility reorients keratin filaments, directing force to desmoplakin, potentially extending its N-terminal plakin domain.
- Desmoplakin exhibits similar force-dependent conformational changes in cardiomyocytes, influenced by myofibril orientation.
Conclusions:
- Desmoplakin is mechanosensitive, with its structural state reflecting transmitted forces.
- Keratin networks mediate force transmission from the actomyosin cytoskeleton to desmosomes.
- These findings provide insights into desmosome mechanobiology across different cell types.
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