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Related Concept Videos

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Tight Junctions

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Tight junctions are molecular seals between cells that prevent the leaking of fluids, ions, and other small solutes across cavities and compartments in multicellular organisms. They are mainly composed of claudin and occludin transmembrane proteins, and other proteins such as tricellulin and JAM (junctional adhesion molecule). All these proteins are 4-pass transmembrane proteins, except JAM, which is a single-pass transmembrane protein belonging to the immunoglobulin superfamily. The...
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Erythropoietin-producing hepatocellular carcinoma receptor (Eph) and its ligand, Eph receptor-interacting protein (Ephrin) were first discovered in the human carcinoma cell line, hence the name. Ephrin-Eph interaction guides cells to reach their appropriate location in adult tissues. They also play an essential role in the immune system by helping in immune cell migration, adhesion, and activation. Based on their structure and function, Eph is divided into two classes — EphA and EphB.
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Tension Response at Adherens Junctions01:26

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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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Cell-matrix's Response to Mechanical Forces01:13

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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 intestinal epithelial lining rapidly renews every 4 to 5 days. The renewal is facilitated by intestinal stem cells (ISCs) located at the base of the crypt– a gland located at the bottom of each villus. ISCs divide asymmetrically to form new stem cells and progenitor daughter cells. The daughter cells are called transit-amplifying (TA) cells which move upwards along the crypt and either differentiate into absorptive cells– the enterocytes or secretory cells– including the...
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Sensing of Barrier Tissue Disruption with an Organic Electrochemical Transistor
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Epithelial tension controls intestinal cell extrusion.

Daniel Krueger1,2, Willem Kasper Spoelstra3, Dirk Jan Mastebroek1

  • 1Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and University Medical Centre Utrecht (UMC), Utrecht, Netherlands.

Science (New York, N.Y.)
|September 4, 2025
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Summary

Cell extrusion in the intestine is regulated by a mechanical "tug-of-war" between cells, not crowding. Cells unable to maintain tension are extruded, ensuring epithelial barrier integrity.

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Area of Science:

  • Cell biology
  • Biophysics
  • Gastroenterology

Background:

  • Epithelial self-renewal is crucial for intestinal homeostasis.
  • Cell extrusion, a key process, was previously thought to be triggered by cell crowding.
  • The precise mechanism regulating cell extrusion remains incompletely understood.

Purpose of the Study:

  • To investigate the mechanical regulation of cell extrusion in the intestinal epithelium.
  • To elucidate the role of intercellular mechanics in maintaining epithelial barrier function.
  • To challenge the prevailing model of crowding-induced extrusion.

Main Methods:

  • Quantitative live microscopy of mouse intestines and organoids.
  • Optogenetic induction of tissue tension.
  • Genetic perturbation of myosin II activity.
  • Local disruption of the basal cortex.

Main Results:

  • A dynamic actomyosin network generates tension across intestinal villi, including the tip.
  • Cell extrusion is regulated by a local
  • tug-of-war
  • between contractile cells.
  • Mechanically weak cells, unable to sustain tension, are extruded.

Conclusions:

  • Intercellular mechanical tension, not just crowding, is a primary driver of cell extrusion.
  • Epithelial barrier integrity is fundamentally dependent on the mechanical properties of cells.
  • This study reveals a novel mechanism for maintaining intestinal tissue homeostasis.