25 Apr 2025
When motile immune cells move through tissue, they are exposed to strong forces. Researchers at LMU have discovered how these cells protect a sensitive organelle, the centrosome, from being destroyed.
Investigating the entire cell structure: Madeleine T. Schmitt and Jörg Renkawitz. | © Daniela Diefenbacher / BMC
Faced with an infection, cells of the immune system have to quickly multiply in order to effectively combat pathogens. And they have to squeeze through narrow pores to reach bacteria or viruses at the site of infection.
In doing so, they can be exposed to strong mechanical forces. It is two proteins in the cell interior that safeguard the centrosome from being damaged by these forces, as researchers led by Dr. Jörg Renkawitz report in Science Advances. Renkawitz leads the independent “Cell & Mechano Biology of the Immune System” research group at LMU’s Biomedical Center Munich (BMC).
On the background: When immune cells squeeze through narrow tissue gaps or traverse complex tissue environments, they come under considerable mechanical stress. These deformations put strain on the entire cell structure, but especially the centrosome, an organelle within cells that is not surrounded by a protective membrane.
Centrosomes are small organelles near the cell nucleus that function like an “organizational center” for the cytoskeleton. Or, to be more precise, for microtubules – thin tubes of protein that give the cell stability and assist transport operations within the cell.
“We discovered that the centrosome is exposed to mechanical forces and can even fracture when cells move through narrow or complex environments,” says Renkawitz. “These breakages give rise to several competing microtubule organizational centers, disrupting cell navigation.” The researchers demonstrated that the actin cytoskeleton – an important component of cell structure, which is involved in cell motility and other processes – transfers mechanical forces directly to the centrosome.
In experiments with labeled dendritic cells – a type of white blood cell of the immune system – from mice, the researchers successfully observed and filmed these processes. Particularly in the case of directed motion through narrow tissue structures, the experiments showed how the paired centrioles that form the centrosome parted. This so-called stretching deformation occurred primarily when the cell and its protrusions squeezed through narrow gaps or simultaneously formed several protrusions to search for a suitable pathway.
Pretty tight: Cells under mechanical stress. Capture: Renkawitz Group
Next, the researchers silenced two genes in immune cells to find out whether they have protective properties. Both genes code for proteins associated with the centrosome: the protein kinase Dyrk3 (dual specificity tyrosine-phosphorylation-regulated kinase 3) and the protein cNAP1 (centrosomal Nek2-associated protein 1).
The results showed that if the proteins were absent, the centrosome became unstable and rapidly came apart under mechanical stress. This resulted in significant disruptions to the directed movements of the cells – an indicator that these proteins play a crucial role in the protective mechanism of the centrosome. “These discoveries show that cells actively protect their internal structures – especially organelles like the centrosome – against mechanical stress,” explains Madeleine T. Schmitt from Renkawitz’s research group, lead author of the paper.
As almost all cells are subject to mechanical forces, whether through motion, pressure, or deformation, this mechanism could be of fundamental importance. For motile cell types such as immune cells and cancer cells in particular, the stability of the centrosome and other cell organelles could be crucial for their function and mobility.
In the longer term, Renkawitz sees the possibility of making motile cancer cells sensitive to mechanical forces by impairing the stability of their organelles, such as the centrosome, and thus driving them into cell death. This may represent a novel therapeutical principle.
Madeleine T. Schmitt, Janina Kroll, Mauricio J.A. Ruiz Fernandez, Robert Hauschild, Shaunak Ghosh, Petra Kameritsch, Jack Merrin, Johanna Schmid, Kasia Stefanowski, Andreas W. Thomae, Jingyuan Chen, Gamze Naz Öztan, Peter Konopka, Germán Camargo Ortega, Thomas Penz, Luisa Bach, Dirk Baumjohann, Christoph Bock, Tobias Straub, Felix Meissner, Eva Kiermaier, Jörg Renkawitz: Protecting Centrosomes from Fracturing Enables Efficient Cell Navigation. Science Advances, 2025