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In animal cells, the extracellular matrix allows cells within tissues to withstand external stresses and transmits signals from the outside of the cell to the inside. The extracellular matrix is extensive, and its composition varies between different types of tissues. For example, the reticular fibers and ground substance make up the ECM in loose connective tissue, while collagen and bone minerals make up the ECM of bone tissue. 
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The adherens junctions that anchor cells together are multi-protein complexes that dynamically adapt to mechanical stimuli such as tensile forces and shear stress. Mechanosensory proteins in these junctions can sense such mechanical stimuli and undergo a shift in their conformation, resulting in an altered function — a process called mechanotransduction.
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Strong contact points between adjacent cells anchor them to each other, forming tissues. Such anchoring junctions are of two types –  adherens junctions and desmosomes. Adherens junctions are abundant in tissues such as  epithelium and endothelium, forming a continuous zone of adhesion called the adhesion belt. In other tissues, such as  heart muscle, they appear as clusters, linking the cells to produce coordinated heart muscle contraction.
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An Efficient and Flexible Cell Aggregation Method for 3D Spheroid Production
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Altering Cell Junctional Tension in Spheroids through E-Cadherin Engagement Modulation.

Seong Ho Kim1, Isaac T S Li1

  • 1Department of Chemistry, The University of British Columbia, Kelowna, British Columbia V1 V 1 V7, Canada.

ACS Applied Bio Materials
|May 10, 2024
PubMed
Summary
This summary is machine-generated.

Researchers developed novel tension gauge tethers (TGTs) to precisely control cell-cell adhesion and mechanical forces within 3D spheroid models, advancing epithelial integrity studies.

Keywords:
DNA tension sensorE-cadherinintercellular adhesionspheroidtension modulation

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Area of Science:

  • Cell Biology
  • Biophysics
  • Biomaterials

Background:

  • Cadherin-mediated tension at adherens junctions (AJs) is crucial for cell adhesion and epithelial integrity.
  • Existing 3D multicellular models lack precise methods for manipulating AJs and quantifying junctional tension.

Purpose of the Study:

  • To introduce a novel system for precise manipulation and quantification of junctional tension in 3D spheroid models.
  • To investigate the role of E-cadherin-mediated adhesion in maintaining cellular mechanics within spheroids.

Main Methods:

  • Development of E-cadherin-modified tension gauge tethers (TGTs) for 3D spheroids.
  • Utilizing DNA triggers for modulation of junctional tension.
  • Employing rupture-induced fluorescence to measure mechanical forces.
  • Applying toehold-mediated strand displacement to disrupt cell-cell adhesion.

Main Results:

  • Successfully measured mechanical forces within 3D spheroids using rupture-induced fluorescence.
  • Demonstrated that mechanically robust TGTs can sustain normal E-cadherin-mediated adhesion.
  • Showcased the ability to disrupt E-cadherin-specific cell-cell adhesion, altering intracellular tension.

Conclusions:

  • The developed TGT system provides a robust and precise method for manipulating cell-cell adhesion and intracellular mechanics in spheroid models.
  • This advancement facilitates deeper understanding of the mechanical regulation of epithelial integrity and cell-cell interactions.