Highly complex processes always take place in our body to monitor for pathogens: T cells of our immune system are busy detecting antigens – suspicious molecules that respond directly in specific receptors of the T cells as a key into a lock. This activates the T-cell and the protective mechanisms of the immune system are activated.
How this process occurs at the molecular level is not yet well understood. What is clear now, however, is that it is not only chemistry that plays a role in blackening antigens to the T-cell; micromechanical effects are also important. Cell surface submicrometer structures act as microscopic compression springs. The resulting tiny forces tend to be extremely important for the identification of antigens. At TU Wien, it was now possible to observe these forces directly using fully developed microscopy methods.
This was made possible by a collaboration between TU Wien, Humbold Universität Berlin, ETH Zurich and MedUni Vienna. The results are now published in the scientific journal “Nano Letters“.
Smell and feel
In terms of physics, our human sensory organs work in completely different ways. We can smell, ie find materials chemically, and we can rub, ie sort objects according to the mechanical resistance they give us. It is similar to T cells: they recognize the specific structure of some molecules, but they can also “feel” antigens mechanically.
“There are microvilli called T cells, which are tiny structures that resemble tiny stems,” says Dr. Gerhard Schütz, head of the biology working group at the Institute of Applied Physics at TU Wien. As the experiments have shown, amazing effects can occur when these microvilli come in contact with an object: The microvilli can penetrate the object, similar to a pencil sharpened finger. They can then even expand, so that the branch-like protrusion becomes the long cylinder, which is rotated over the object.
“Tiny forces occur in the process, on an order of magnitude smaller than nanonewton,” says Gerhard Schütz. One nanonewton corresponds largely to the pressure force that would come with water droplets with a diameter of one twentieth of a millimeter.
Measure force in the hydrogel
Measuring such small forces is a challenge. “We successfully combine the cell with tiny test beads in a specially developed gel. The beads carry molecules on their surface to which the T cell regenerates. answer, “Gerhard Schütz explained. “If we know the effect of our gel on the beads and measure how far the beads move near the T-cell, we can work out the force of the beads. work between the T-cell and the beads. “
These tiny forces and the behavior of the microvilli tend to play an important role in identifying the molecules and thus stimulating an immune response.
We know that biomolecules as proteins exhibit different behaviors when deformed by mechanical forces or when bonds are simply torn. Such devices appear to play a role in antigen recognition, and with our measurement techniques this can be studied in detail for the first time. “
Professor Gerhard Schütz, TU Wien
Source:
Vienna University of Technology
Magazine Reference:
Aramesh, M., et al. (2020) Applied Bead Evaluation to Measure Three-dimensional Traction Forces at T-Cell Activation. Nano Letters. doi.org/10.1021/acs.nanolett.0c03964.