Novel
microcopy methods allow scientists to study the mechanical interaction of
T-cells and particles. Credit: Vienna University of Technology.
When
T-cells of our immune system become active, tiny traction forces at the
molecular level play an important role. They have now been studied at TU Wien.
Highly
complicated processes constantly take place in our body to keep pathogens in
check: The T-cells of our immune system are busy searching for antigens—suspicious
molecules that fit exactly into certain receptors of the T-cells like a key
into a lock. This activates the T-cell and the defense mechanisms of the immune
system are set in motion.
How this
process takes place at the molecular level is not yet well understood. What is
now clear, however, is that not only chemistry plays a role in the docking of
antigens to the T-cell; micromechanical effects are important too.
Submicrometer structures on the cell surface act like microscopic tension springs.
Tiny forces that occur as a result are likely to be of great importance for the
recognition of antigens. At TU Wien, it has now been possible to observe these
forces directly using highly developed microscopy methods.
This was
made possible by a cooperation between TU Wien, Humbold Universität Berlin, ETH
Zurich and MedUni Vienna. The results have now been published in the scientific
journal Nano Letters.
Smelling
and feeling
As far as
physics is concerned, our human sensory organs work in completely different
ways. We can smell, i.e. detect substances chemically, and we can touch, i.e.
classify objects by the mechanical resistance they present to us. It is similar
with T cells: they can recognize the specific structure of certain molecules,
but they can also 'feel' antigens in a mechanical way.
"T
cells have so-called microvilli, which are tiny structures that look like
little hairs," says Prof. Gerhard Schütz, head of the biophysics working
group at the Institute of Applied Physics at TU Wien. As the experiments
showed, remarkable effects can occur when these microvilli come into contact
with an object: The microvilli can encompass the object, similar to a curved
finger holding a pencil. They can then even enlarge, so that the finger-like
protrusion eventually becomes an elongated cylinder, which is turned over the
object.
"Tiny
forces occur in the process, on the order of less than a nanonewton," says
Gerhard Schütz. One nanonewton corresponds roughly to the weight force that a
water droplet with a diameter of one-twentieth of a millimeter would exert.
Force
measurement in the hydrogel
Measuring
such tiny forces is a challenge. "We succeed by placing the cell together
with tiny test beads in a specially developed gel. The beads carry molecules on
their surface to which the T cell reacts," explains Gerhard Schütz.
"If we know the resistance that our gel exerts on the beads and measure
exactly how far the beads move in the immediate vicinity of the T-cell, we can
calculate the force that acts between the T-cell and the beads."
These tiny
forces and the behavior of the microvilli are likely to be important in
recognizing the molecules and thus triggering an immune response. "We know
that biomolecules such as proteins show different behavior when they are
deformed by mechanical forces or when bonds are simply pulled," says
Gerhard Schütz. "Such mechanisms are also likely to play a role in antigen
recognition, and with our measurement methods this can now be studied in detail
for the first time."