Hungry immune cells: Physicists in Bayreuth are investigating the transport routes of pathogens
University of Bayreuth, Presse Release No. 148/2017, 6 December 2017
When bacteria, viruses, and other particles make it into the bodies of humans and animals, the immune system is generally able to render these pathogens innocuous. A certain type of immune cell plays an integral role in this process: macrophages are phagocytes that ingest foreign particles and break them down such that they no longer represent a danger to the organism. Physicists at the University of Bayreuth led by Prof. Dr. Holger Kreß have now published in Scientific Reports their new findings relating to these processes. It turns out that the size of the particle plays a crucial role in determining how the immune cell deals with it.
Light microscope image of a macrophage (immune cell) with “ingested” particles. These are marked with different coloured lines according to their diameter: green = 3 micrometres, blue = 2 micrometres, orange = 1 micrometre. - © Steve Keller
Size matters: How phagocytes react to foreign bodies
The researchers in Bayreuth used tiny plastic beads as the particles in their experiments on the cell lines of mice. On the surfaces of the beads, the team placed antibodies that often occur in nature: Immunoglobulin G (IgG). This ensured that the macrophages reacted to these foreign particles as if they were actually dangerous bacteria.
Particles with a diameter of around three micrometres are relatively large. As soon as they reach the interior of the immune cell, they are a quickly transported towards the cell nucleus, where in living organisms they are usually digested more quickly than at the cell periphery. In medium-sized particles, this process is more sluggish.
Diagram of the size-dependent transport of particles. Large particles (3 micrometres) are quickly transported from the periphery of the cell to the centre. Small particles (1 micrometre) display considerably more erratic movements with many transport phases back to the cell periphery. - © Steve Keller
Small particles with a diameter of around one micrometre, on the other hand, display a conspicuous "indecisiveness": Once they have finally made it near the cell nucleus, they often go back to the cell periphery. "This process may support the disposal of digestive waste that is channelled out of the cell," said Prof. Kreß.
In view of these size-dependent differences, the team of scientists investigated which parts of the immune cell initiate and encourage transport movements in different directions. "When large particles move to the cell nucleus, a certain protein – dynein – plays a crucial role. It is an important motor for this transport movement. In contrast, tiny fibres consisting of the protein actin play an integral role in the much less regular transport of smaller particles," explained Steve Keller (Dipl.-Phys.), doctoral researcher and lead author of the new study.
Fluorescence microscope image of a macrophage with its cell nucleus coloured in blue and its microtubules coloured in red. These serve as “tracks” on which the molecular motors such as dynein transport the particles. - © Steve Keller
Valuable clues for the encapsulation of medical substances
The primary objective of the experiments was to gain a deeper understanding of the processes that are responsible for making the immune cell destroy antibody-coated pathogens. However, some possible applications are already emerging. "Drug delivery" is a process that is being used more and more in medicine in which substances are encased in capsules and transported to the place within the organism where it is supposed to be released and have an effect. The team of scientists in Bayreuth thinks the fact that a particle's size seems to determine how immune cells deal with it could provide an interesting starting point for the optimal design of capsules.
Overlay of the two microscopic images of a macrophage. The particles in the interior of the cell are marked with different colours according to their diameter: green = 3 micrometres, blue = 2 micrometres, orange = 1 micrometre. - © Steve Keller
Holographic optical tweezers in use
The findings published in Scientific Reports would not have been possible without a combination of various biophysical techniques. For example, the researchers used "holographic optical tweezers" to hold the antibody-coated particles in place and position them so close to the immune cells that they could be identified as putative pathogens and ingested. This technique makes use of an optical microscope in conjunction with laser beams: The effect of the light beam alone allows certain particles to be captured and moved precisely to the desired location. In addition, "magnetic tweezers" enabled the scientists to interrupt transport movements within the cell and shed light on which proteins are involved in these processes and what role they play.
Steve Keller, Dipl.-Phys. (left) and Prof. Dr. Holger Kreß (right) preparing an experiment at a microscope with holographic optical tweezers. Photo: Christian Wißler.
Steve Keller, Konrad Berghoff and Holger Kreß, Phagosomal transport depends strongly on phagosome size,
Scientific Reports 7, Article number: 17068 (2017),
Prof. Dr. Holger Kreß
Biological Physics Group
Department of Physics
University of Bayreuth
Phone: +49 (0)921 / 55-2505
University of Bayreuth
Universitätsstr. 30 / ZUV
Phone: +49 (0)921 / 55-5356