Abstract
Cell-cell junctions are critical structures in a number of tissues for mechanically coupling cells together, cell-to-cell signaling, and establishing a barrier. In many tissues, desmosomes are an important component of cell-cell junctions. Loss or impairment of desmosomes presents with clinical phenotypes in the heart and skin as cardiac arrhythmias and skin blistering, respectively. Because heart and skin are tissues that are subject to large mechanical stresses, we hypothesized that desmosomes, similar to adherens junctions, would also experience significant tensile loading. To directly measure mechanical forces across desmosomes, we developed and validated a desmoglein-2 (DSG-2) force sensor, using the existing TSmod Förster resonance energy transfer (FRET) force biosensor. When expressed in human cardiomyocytes, the force sensor reported high tensile loading of DSG-2 during contraction. Additionally, when expressed in Madin-Darby canine kidney (MDCK) epithelial or epidermal (A431) monolayers, the sensor also reported tensile loading. Finally, we observed higher DSG-2 forces in 3D MDCK acini when compared to 2D monolayers. Taken together, our results show that desmosomes experience low levels of mechanical tension in resting cells, with significantly higher forces during active loading.
Highlights
Strong cell-cell junctions, formed by adherens junctions and desmosomes, are critical to the integrity of cellular tissues, including the ability to resist mechanical stress
Others, have used force biosensor techniques to directly show that the adherens junction is a major load bearing structure [3,4], other cell-cell junctional structures, such as desmosomes, have not yet been directly studied with force biosensors to determine if these components are load bearing
Our results, showing that DSG-2, a desmosomal cadherin, bears mechanical tension, represents the first report to directly demonstrate that the desmosome is a load-bearing structure
Summary
Strong cell-cell junctions, formed by adherens junctions and desmosomes, are critical to the integrity of cellular tissues, including the ability to resist mechanical stress. Using Förster resonance energy transfer (FRET)-based tension biosensors, we and others have shown that mechanical tension is applied across actin-connected cadherins in adherens junctions [3,4]. It is not known if other components of the cell-cell junction, such as desmosomes, experience mechanical force. Desmosomes are intermediate filament (IF)-connected structures found in epithelial and muscle tissues that bind cells together. These junctions consist of a transmembrane desmosomal cadherin (desmocollin or desmoglein) connected to intermediate filaments by linker proteins, Cells 2018, 7, 66; doi:10.3390/cells7070066 www.mdpi.com/journal/cells
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