The precise mechanics of cell movement are finally revealed
Cell movement is a critical process during the body’s development, as differentiated cells must make their way to specific tissues. Cells also mobilize to repair wounds and fight infections. Meanwhile, cancer cells move to nearby blood vessels to spread to other parts of the body.
The speed of cell movement, or cell velocity, is controlled by how sticky the surface is beneath it. However, the exact mechanisms underlying cell movement and velocity have remained a mystery for decades.
To investigate, experts at the Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC) developed a new mathematical model. The researchers have finally captured, for the first time, the precise mechanics and forces involved in cell movement.
“The mathematical model we developed can now be used by researchers to predict how different cells will behave on various substrates,” said study co-lead author Professor Martin Falcke. “Understanding these basic movements in precise detail could provide new targets to interrupt tumor metastasis.”
In collaboration with experimental physicists at Ludwig Maximilians Universität München, a team of theoretical physicists at MDC tracked the speed of more than 15,000 cancer cells as they moved along narrow lanes on a sticky surface. The stickiness of the surface alternated between low and high, which allowed the experts to observe what happens as a cell transitions between dynamic stickiness levels like those present in the human body.
Professor Falcke and PhD student Behnam Amiri used the large dataset to develop a mathematical equation that represents the factors involved in cell movement.
“Previous mathematical models trying to explain cell migration and motility are very specific, they only work for one feature or cell type,” said Amiri. “What we tried to do here is keep it as simple and general as possible.”
The model not only matched the data gathered at LMU, but was also validated by measurements of various other cell types taken over the past 30 years. “This is exciting,” said Professor Falcke. “It’s rare that you find a theory explaining such a large spectrum of experimental results.”
During movement, a cell pushes out its membrane in the direction it is traveling while expanding an internal network of actin filaments. The cell peels off its back end, and the speed at which this occurs depends on adhesion bonds between the cell and the surface beneath it.
The actin network needs friction to mobilize the cell. This means that when there are no adhesive bonds, the cell struggles to move because the actin network does not have anything to push off against.
“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,” explained Professor Falcke.
More friction is created as the number of bonds increase, and the cell can generate more force. The cell can then move faster, until the point when it is too sticky to swiftly pull off its back end, and the cell slows down again.
The researchers investigated what happens when the front and back ends of the cell experience different levels of stickiness. They were especially interested in what happens when it is stickier under the back end of the cell than the front. Would the cell get stuck if it cannot generate enough force to pull off the back end? The experts determined that the cell may get slowed way down, but does not get stuck.
Professor Falcke said the most challenging part was to wrap his mind around the fact that this mechanism works only with friction forces, because there is nothing for the cell to firmly latch onto. The friction-like forces are what allows the cell to keep moving, even when bonds are stronger in the back than in the front. In this case, the cell slowly peeled 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,” said Professor Falcke. “This is how the cell keeps itself from getting stuck.”
The findings provide new insight for developmental biology, as well as for potential cancer treatments. Currently, the team is investigating how cells move in two dimensions, including how they make hard right and left turns and U-turns.
The study is published in the journal Proceedings of National Academy of Science.
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