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Tension Gauge Tether Probes for Quantifying Growth Factor Mediated Integrin Mechanics and Adhesion
Published on: February 11, 2022
Defining single molecular forces required to activate integrin and notch signaling
1Department of Physics, Center for the Physics of Living Cells and Institute for Genomic Biology University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
Science (New York, N.Y.)
|May 25, 2013
Summary
Researchers developed a new method to measure the forces cells use to interact with their environment. They found cells apply about 40 piconewtons to integrin-ligand bonds and less than 12 pN to activate Notch receptors.
Area of Science:
- Cellular mechanics
- Molecular biology
- Biophysics
Background:
- Cellular functions and multicellular development rely on mechanical interactions via membrane receptors.
- Understanding single-molecule forces is crucial for deciphering receptor-ligand signaling pathways.
Purpose of the Study:
- To develop a method for measuring the precise forces required to activate single ligand-receptor bonds.
- To quantify the mechanical forces cells exert during initial adhesion and receptor activation.
Main Methods:
- Developed the tension gauge tether (TGT) approach, immobilizing ligands via a rupturable tether.
- Utilized tethers with tunable tension tolerances to restrict receptor-ligand tension.
- Applied TGT to measure forces on integrin-ligand bonds and Notch receptors.
Main Results:
- Cells apply a universal peak tension of approximately 40 piconewtons (pN) to single integrin-ligand bonds during initial adhesion.
- Activation of Notch receptors requires less than 12 pN of force.
- The TGT approach can provide defined molecular mechanical cues to regulate cellular functions.
Conclusions:
- The TGT method accurately measures single-molecule forces in cellular adhesion and signaling.
- Specific force thresholds are critical for the activation of key cellular receptors like integrins and Notch.
- This technique offers a new tool for investigating mechanotransduction and controlling cellular behavior.
Related Concept Videos
01:15Activation of Integrins
Integrins bind ligands and transmit information from outside the cell to inside or vice-versa through an "outside-in signaling" or "inside-out signaling."
In "outside-in signaling," external factors in the extracellular space bind to exposed ligand binding sites on integrins. This causes the inactive protein to undergo a conformational change to become active. Integrins are often clustered on the cell membrane. Repetitive and regularly spaced ligand binding events provide an effective stimulus.
In "outside-in signaling," external factors in the extracellular space bind to exposed ligand binding sites on integrins. This causes the inactive protein to undergo a conformational change to become active. Integrins are often clustered on the cell membrane. Repetitive and regularly spaced ligand binding events provide an effective stimulus.
01:17Intracellular Signaling Affects Focal Adhesions
Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
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03:14Notch Signaling Pathway
The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
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03:14Notch Signaling Pathway
The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
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01:10Integrins
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Some ECM proteins assemble into a basement membrane to which the remaining components adhere. Proteoglycans typically form the bulk of the ECM while fibrous proteins, like collagen,...
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01:13Cell-matrix's Response to Mechanical Forces
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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