22-Jan-2021 - Max-Delbrück-Centrum für Molekulare Medizin (MDC) Berlin-Buch

How cells move and don’t get stuck

New insight for developmental biology and potential cancer treatment

Theoretical physicists from Berlin teamed up with experimental physicists from Munich to determine the precise mechanics involved in cell motility.

Cell velocity, or how fast a cell moves, is known to depend on how sticky the surface is beneath it, but the precise mechanisms of this relationship have remained elusive for decades. Now, researchers from the Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC) and Ludwig Maximilians Universität München (LMU) have figured out the precise mechanics and developed a mathematical model capturing the forces involved in cell movement. The findings, reported in the journal Proceedings of the National Academy of Sciences (PNAS), provide new insight for developmental biology and potential cancer treatment.

Cell movement is a fundamental process, especially critical during development when cells differentiate into their target cell type and then move to the correct tissue. Cells also move to repair wounds, while cancer cells crawl to the nearest blood vessel to spread to other parts of the body.

“The mathematical model we developed can now be used by researchers to predict how different cells will behave on various substrates,” says Professor Martin Falcke, who heads MDC’s Mathematical Cell Physiology Lab and co-led the research. “Understanding these basic movements in precise detail could provide new targets to interrupt tumor metastasis.”

Teaming up to pin down

The finding comes thanks to experimental physicists at LMU teaming up with theoretical physicists at MDC. The experimentalists, led by Professor Joachim Rädler, tracked how quickly more than 15,000 cancer cells moved along narrow lanes on a sticky surface, where the stickiness alternated between low and high. This allowed them to observe what happens as the cell transitions between stickiness levels, which is more representative of the dynamic environment inside the body.

Then, Falcke and Behnam Amiri, co-first paper author and Ph.D. student in Falcke’s lab, used the large dataset to develop a mathematical equation that captures the elements shaping cell motility.

“Previous mathematical models trying to explain cell migration and motility are very specific, they only work for one feature or cell type,” Amiri says. “What we tried to do here is keep it as simple and general as possible.”

The approach worked even better than expected: the model matched the data gathered at LMU and held true for measurements about several other cell types taken over the past 30 years. “This is exciting,” Falcke says. “It’s rare that you find a theory explaining such a large spectrum of experimental results.”

Friction is key

When a cell moves, it pushes out its membrane in the direction of travel, expanding an internal network of actin filaments as it goes, and then peels off its back end. How fast this happens depends on adhesion bonds that form between the cell and the surface beneath it. When there are no bonds, the cell can hardly move because the actin network doesn’t have anything to push off against. The reason is friction: “When you are on ice skates you cannot push a car, only when there is enough friction between your shoes and the ground can you push a car,” Falcke says.

As the number of bonds increase, creating more friction, the cell can generate more force and move faster, until the point when it is so sticky, it becomes much harder to pull off the back end, slowing the cell down again.

Slow, but not stuck

The researchers investigated what happens when the front and rear ends of the cell experience different levels of stickiness. They were particularly curious to figure out what happens when it is stickier under the back end of the cell than the front, because that is when the cell could potentially get stuck, unable to generate enough force to pull off the back end.

This might have been the case if the adhesion bonds were more like screws, holding the cell to the substrate. At first, Falcke and Amiri included this type of “elastic” force in their model, but the equation only worked with friction forces.

“For me, the most challenging part was to wrap my mind around this mechanism working only with friction forces,” Falcke says, because there is nothing for the cell to firmly latch onto. But it is the friction-like forces that allow the cell to keep moving, even when bonds are stronger in the back than the front, slowly peeling itself off like scotch tape. “Even if you pull just a little with a weak force, you are still able to peel the tape off – very slowly, but it comes off,” Falcke says. “This is how the cell keeps itself from getting stuck.”

The team is now investigating how cells move in two dimensions, including how they make hard right and left turns, and U-turns.

Facts, background information, dossiers

  • cell motility
  • cells
  • developmental biology
  • cancer therapy

More about MDC

  • News

    Tracking RNA through space and time

    A research team at the MDC has succeeded in tracking genes through space and time within a one-cell zebrafish embryo – even before cell division occurs. They have now described a method in the journal “Nature Communications” that may one day allow scientists to measure cell response to drug ... more

    How the immune system paves the way for SARS-CoV-2

    The immune system actually wants to fight SARS-CoV-2 with antiviral signaling molecules. But a research team from Charité and MDC has now shown how such a signaling molecule can promote the replication of the virus. Most people infected with SARS-CoV-2 are able to recover from the disease a ... more

    A potent weapon against lymphomas

    MDC researchers have developed a new approach to CAR T-cell therapy. The team has shown in Nature Communications that the procedure is very effective, especially when it comes to fighting follicular lymphomas and chronic lymphocytic leukemia, the most common type of blood cancer in adults. ... more

More about LMU

  • News

    Catabolic Processes in Cells: Controlling the Danger Within

    Trillions of cells in our body work non-stop to keep us alive. This generates waste that is decomposed in specialized cellular organs. But what happens if the cellular trash cans don't work? Researchers assume that this is the cause of numerous diseases. Biologists at the University of Duis ... more

    Highly Responsive Immune Cells Seem to be Beneficial for the Brain

    Findings by researchers from Germany support the view that hyperactive immune cells in the brain can have a protective effect in the course of neurodegenerative diseases. Experts from Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Ludwig-Maximilians-Universität München (LMU) a ... more

    COVID-19: Breakthrough infection can substitute for a third vaccine shot

    According to a new study led by Ulrike Protzer, a breakthrough infection after two vaccinations achieves the same protective effect as an additional booster vaccination. According to the study by Helmholtz Munich, LMU and TUM, the decisive factor for immunity is that the immune system has h ... more

  • Authors

    Prof. Dr. Thomas Carell

    Thomas Carell graduated in chemistry, completing his doctorate at the Max Planck Institute for Medical Research under the tutelage of Prof. Dr Dr H. A. Staab. Following a research position in the USA, he accepted a position at ETH Zurich, setting up his own research group in the Laboratory ... more

q&more – the networking platform for quality excellence in lab and process

The q&more concept is to increase the visibility of recent research and innovative solutions, and support the exchange of knowledge. In the broad spectrum of subjects covered, the focus is on achieving maximum quality in highly innovative sectors. As a modern knowledge platform, q&more offers market participants one-of-a-kind networking opportunities. Cutting-edge research is presented by authors of international repute. Attractively presented in a high-quality context, and published in German and English, the original articles introduce new concepts and highlight unconventional solution strategies.

> more about q&more

q&more is supported by: