The chemicals that cells leach onto their path may determine how far they can crawl.
Cells crawl for many reasons, including to help heal a wound聽or, in the case of cancer cells, to metastasise. But scientists still have a relatively poor understanding of what determines how far a cell can travel or what route it will take.
at Johns Hopkins University in Maryland and his colleagues wanted to investigate whether the chemicals that a cell releases as it moves, including certain proteins, were part of the puzzle.
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They were inspired by earlier experiments with crawling cells conducted by some members of their team. Here, the researchers recorded mammalian 鈥淢adin-Darby canine kidney鈥� cells as they crawled on narrow strips of a sticky protein. Instead of immediately travelling the full length of the strip in one go, the cells travelled forward a short distance and then retreated, before moving a little farther forward and retreating again, and so on.
鈥淏ut if you let the cells crawl all over the place for a long time, and then take them off and put down new cells, the new cells manage to just crawl all the way from one side to the other,鈥� says , also at Johns Hopkins University, who worked on the study. 鈥淲e wanted to figure out what is going on with that.鈥�
Their idea was that the interactions between a cell and the chemical footprint it leaves on a surface make the cell鈥檚 鈥渇ront鈥� and 鈥渂ack鈥� ends more chemically distinct, strengthening its polarity. They conjectured that if a cell moves onto part of a surface that is not sufficiently coated in its chemical trail, its polarity decreases. This prompts it to head towards areas that are already covered, where touching the chemicals ramps the cell鈥檚 polarity back up. When the researchers simulated this idea on a computer, it matched the way that the cells crawled on the narrow protein strips in the experiments.
In simulation, cells that crawled on wider, two-dimensional surfaces could take on a whole range of crawling routes depending on the rate at which they were secreting the chemical footprint, says Perez Ipi帽a. When he and his colleagues simulated cells depositing a chemical footprint at a low rate, the cells would get stuck moving in small circles on one part of the surface. When they simulated faster footprint deposition, the cells explored a lot more widely.
鈥淒epending on how easy it is for them to create a footprint, that makes it easier for them to blaze new trails,鈥� says Camley.
at the Institute of Science and Technology Austria, who wasn鈥檛 involved in the analysis, says visualising the proteins that make up cells鈥� footprints under a microscope is difficult, so biophysical models and computer simulations can help researchers infer some of the rules for how they crawl. The new study provides one such model, which is valuable because it matches past observations and predicts what cells might do when given more space to roam, he says.
However, the experiments performed so far may have limited predictive value, says at the Technical University of Denmark, who wasn鈥檛 involved in the new study. That鈥檚 because they involved removing living cells from their natural environment, where there might be many other chemicals that influence their movement.
Camley says cells in living tissues are susceptible to cues from electromagnetic fields or chemicals produced by other cells. But scientists will have to explore how those signals compete with the cells鈥� footprints and determine the ways they move by developing more complex experiments and models in the future.
bioRxiv
