About this item:

131 Views | 97 Downloads

Author Notes:

Correspondence: dconway@vcu.edu; Tel.: +1-804-828-2592

S.R.B., A.P.K., and D.E.C. designed the tension sensor; S.R.B., P.T.A., V.N., N.R.D., C.R.M., S.T.N., D.A.A., A.M., and D.E.C. performed experiments and analyzed data; and D.E.C. wrote the article.

We thank Kathy Green and Rob Tombes for providing reagents and Niharika Patel and Hayley Eicher for assistance with experiments.

We also wish to thank Scott Henderson and Judy Williamson in the VCU Microscopy Core for performing immunogold electron microscopy.

The authors declare no conflict of interest.

Subjects:

Research Funding:

This project was supported by start-up funding from the VCU Presidential Research Quest Fund (to DEC), American Heart Association 16SDG27370007 (to DEC), and National Institutes of Health (NIH) grants R03AR068096 (to DEC), R35GM119617 (to DEC), and R01AR048266 (to APK).

Services and products in support of the research project were generated by the VCU Massey Cancer Center Biological Macromolecule Shared Resource and the Microscopy Shared Resource, both supported, in part, with funding from NIH-NCI Cancer Center Support Grant P30 CA016059. APC (article processing charge) was sponsored by MDPI.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Cell Biology
  • desmosomes
  • mechanobiology
  • cell biophysics
  • INTERMEDIATE-FILAMENTS
  • EPITHELIAL-CELLS
  • JUNCTIONS
  • DYNAMICS
  • CYTOSKELETON
  • KERATINOCYTES
  • ACTIVATION
  • TENSEGRITY
  • CONTACTS
  • VINCULIN

The Desmosomal Cadherin Desmoglein-2 Experiences Mechanical Tension as Demonstrated by a FRET-Based Tension Biosensor Expressed in Living Cells

Tools:

Journal Title:

Cells

Volume:

Volume 7, Number 7

Publisher:

, Pages 66-66

Type of Work:

Article | Final Publisher PDF

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.

Copyright information:

© 2018 by the authors.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
Export to EndNote