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Biophysics;
Abstract:
Desmosomes are intercellular adhesion complexes that link the intermediate filament cytoskeletons of neighboring cells. Mutations in desmosomal proteins lead to severe cardiomyopathies and skin blistering diseases, indicating that desmosomes play an essential role in defining tissue mechanical properties. However, how and even whether desmosomes bear tension in living tissues remained unclear. In this study we inserted a Förster resonance energy transfer (FRET)-based tension sensing module (TSM) into both major isoforms of desmoplakin (DPI and DPII), a scaffolding protein that links desmosomal cadherins to intermediate filaments. Live-cell measurements yielded FRET values consistent with negligible mechanical tension transmitted through DPI in confluent monolayers, sparse colonies, and the edge of expanding monolayers of Madin-Darby canine kidney (MDCK) epithelial cells. Analogous measurements indicated negligible tension transmitted through DPII in confluent monolayers of wild-type murine epidermal keratinocytes (MEK) and in MEKs depleted of endogenous DP. External mechanical stretch applied to MDCK and MEK monolayers, however, yielded significant decreases in FRET, consistent with stretch-induced mechanical tension on DP. We suggest that, in epithelia, desmosomes function to protect tissues from mechanical disruption while still allowing the cellular movements and shape changes that are essential in the contexts of tissue homeostasis and collective cell migration.
