How cells move and do not get caught

The speed of a cell, or the speed at which a cell moves, is known to depend on the stickiness of the surface underneath, but the exact ways in which this relationship has been unstable for decades. Now, researchers from the Max Delbrück Center for Molecular Medicine at the Helmholtz Society (MDC) and Ludwig Maximilians Universität München (LMU) have discovered the precise mechanics and developed a mathematical model capturing the forces that is involved in cell migration. The findings, reported in the journal Proceedings of the National Academy of Sciences (PNAS), provides a new perspective for developmental biology and potential cancer treatment.

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

“The mathematical model we have now developed can be used by researchers to predict how different cells behave on different substrates,” says Professor Martin Falcke, who heads Lab MDC Mathematical Cell Epidemiology and co – directed the research. “Understanding these underlying trends in detail could provide new targets to prevent tumor metastasis.”

Team up to pin down

The result comes thanks to experimental physicists at LMU combining theoretical physics at MDC. The testers, led by Professor Joachim Rädler, found that as quickly as more than 15,000 cancer cells moved on narrow layers on a sticky surface, where the sticky fluctuated between low and high. This allows them to monitor what happens as the cells move between sticky stages, which are more representative of the dynamic environment inside the body.

Then, Falcke and Behnam Amiri, co-author of a paper and Ph.D. a student in the Falcke lab, he used the large database to develop a mathematical equation that captures the elements that shape cell motility.

“Previous mathematical models attempt to explain cell migration and motility in a very specific way, they only work for one feature or type of cell,” Amiri says. “What we’ve tried to do here is to keep it as simple and universal as possible.”

The approach worked even better than expected: the model matched the data collected at LMU and kept true for measurements of several other cell types built over the 30 years of the study. gone. “This is inspiring,” Falcke says. “You rarely find a theory explaining such a large spectrum of experimental results.”

Antidepressants are basic

As a cell moves, it pushes out its limbs in terms of travel, expands an inner network of actin filaments as it passes, and then peels off its end. How quickly this happens depends on adhesion bonds forming between the cell and the underlying surface. When there are no bonds, the cell can hardly move because the actin network has nothing to push away. The reason for a collision is: “When you’re on ice skates you can’t push a car, just when there is enough friction between your shoes and the ground you can push a car,” Falcke says.

As the number of bands increases, creating more breakdown, the cell can generate more force and move faster, to the point that when it is so sticky, it becomes much harder at the back end. take it off, slowing down the cell again.

Slowly, but non-stop

The researchers studied what happens when the front and back of the cell get different levels of sticky. They were particularly curious to find out what happens when it is more sticky under the back end of the cell than in the front, because that is when the cell could pass through, unable to generate enough force. to remove the back end.

This may be as if the adhesion bands are more like screws, holding the cell to the substrate. Initially, Falcke and Amiri included the “elastic” force type in their model, but the equation only worked with breaking forces.

“For me, the most challenging part was putting my mind around this approach of working directly with breaking forces,” Falcke says, as there is nothing to connect the cell to But it is the friction-like forces that allow the cell to keep moving, even when the back has stronger bands than the front, pulling itself slowly like scotch tape. you pull just a little bit with a weak force, you can take the tape off – very slowly, but it will come off, “Falcke says. “This is how the cell keeps itself from getting caught.”

The team is now studying how cells move in two dimensions, including how they make right and left hard attempts, and a U-turn.

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