Findings on the mechanical signals behind cell migration – give new clues to cancer research

Associate professor Jakub Sedzinski from the Novo Nordisk Foundation for Stem Cell Medicine, reNEW

The latest findings of reNEW’s Associate Professor Jakub Sedzinski provide new leads for cancer research and targeted medical therapies. “Our discovery could help researchers to find ways to prevent cancer cells from migrating and develop into tumors. It could also be used to steer healthy cells to deliver drugs to a sick tissue,” said Associate Professor Sedzinski.

The descendants of stem cells, progenitor cells, are commonly positioned at the base of tissues. In many organs, however, they have to move or migrate to reach the positions where they are needed. During migration, moving cells use finger-like protrusions to sense the mechanical properties of their neighboring cells.

“Progenitor cells make protrusions so that they can grab other cells and sense their stiffness. We found that they prefer to migrate to regions within the neighboring tissue that are stiffer,” said Associate Professor Sedzinski. Researchers have for many years focused on the biochemical signals that trigger cell migration, but we are only now starting to understand how mechanical signals direct migration. “Our work demonstrates that mechanical signals also play a significant role during cell migration.”

During the migration process, the progenitor cells acquire a specialized function before joining the top layer of the tissue. This target layer eventually develops into a mature organ, the epidermis, as new cells are added to the tissue. The research of Associate Professor Sedzinski and his team focus on the mucous epithelial cells that make up our respiratory tract. This type of cells have cilia, hair-like structures, that push back particles such as bacteria, viruses or other debris when we inhale.

To understand how our respiratory track is built, they work on a model system, the frog embryo, whose epidermis is built using similar strategies to that of the human respiratory system. “We create images of the formation of this epithelial tissue through our microscopes. The migration of the progenitor cell from the base of the tissue to its top takes three to five hours in a lab environment,” Associate Professor Sedzinski explained.

A progenitor cell uses protrusions (in green) to pull on the neighboring cells (in magenta)

Findings provide new leads for cancer research

Cancer cells, just like healthy cells, use protrusions to probe their neighboring environment and migrate. Instead of developing into a healthy specialized tissue, they result in tumor tissue. By understanding how the protrusions used by the (progenitor) cells probe their environment, researchers could find ways to reduce their capacity to build these protrusions. This knowledge could also be used to prevent cancer cells from migrating and eventually develop into tumors. It would immobilize the cancer cells and stop their spread,” said Associate Professor Sedzinski. To reach this stage, researchers must first identify the molecules that control these protrusions.

The findings on the mechanical forces used during cell migration has another potential application. “By understanding how cells move, we could try to steer cells to specific places on the target tissue where it would be beneficial for them to be. They could for instance deliver drugs to an infected tissue or a tumor,” he added.

Multi-disciplinary collaboration behind the discovery

The findings result from a multi-disciplinary collaboration that combined developmental biology and theoretical physics. The international team works at the Novo Nordisk Foundation Center for Stem Cell Research, reNEW, and the Niels Bohr Institute, both part of the University of Copenhagen, and the Max Planck Center for Physics of Complex Systems in Dresden, Germany.

Associate Professor Sedzinski is a principal investigator at reNEW’s Copenhagen node, based at the University of Copenhagen. He has a cross-disciplinary background in biology, biophysics, and computational biology. After undergraduate studies in molecular biology at the University of Wroclaw, Poland, he completed a PhD at the Max Planck Institute of Molecular Cell Biology and Genetics in Dresden. Associate Professor Sedzinski then received a fellowship from European Molecular Biology Organization to carry out research at the University of Texas, Austin. Here, he continued his training in mechanics and regulation of cell shape, but in the context of developing embryos.

Additional details can be found in the article “Multiciliated cells use filopodia to probe tissue mechanics during epithelial integration in vivo” published in nature communications on October 28, 2022.

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