How cells can find their way through the human body
by Bob Yirka , Phys.org
A team of researchers affiliated with multiple institutions in the U.K. has discovered how cells are able to travel so accurately through the human body. In their paper published in the journal Science, the group describes a theory they developed to explain cell orienteering and how they tested it using mazes.
When the body is injured, such as being poked with a needle, the immune system responds by sending white blood cells to kill any bacteria that might be trying to enter through the wound. But how do the cells know how to find the wound? Prior research has shown that cells use chemicals in the body known as chemoattractants to navigate short distances. White blood cells can sense and move toward them—but it only works for short distances. In this new effort, the researchers found that cells can use such chemoattractants in a different way to navigate longer and more complicated pathways.
The researchers theorized that certain cells navigate by breaking down chemoattractants that are close to them. They then sense the degree to which the chemoattractants are replenished, and most importantly, in which direction. By noting the position of the new chemoattractants, they are able to move toward their desired destination. As an example, a white blood cell working its way to a wound upon finding a fork in the road would choose the path with the most or newest chemoattractants after it breaks them down in both directions.
To test their theory, the researchers first created computer models to test its soundness. Doing so convinced them they were on the right track. Next, they etched a host of tiny mazes onto silicon chips, added chemoattractants and then dropped in soil amoebae that are known to navigate. They then watched as the amoebae broke down the chemoattractants they found in their path and then continued on their way in the direction in which new chemoattractants were filling in for the old. They found that the amoebae were very good at finding their way to destinations on relatively simple mazes, but were less skilled in those that were more complicated and had long dead ends. Still, nearly half of those tested managed to find their way through. The researchers suggest the accuracy declines as more time is taken to parse a maze. Those cells at the tail end of a group find all the chemoattractants have already been broken down by those ahead of them, and thus have nothing to use as a guide.
Shows the computer models used work out how cells would behave. The models are excellent – they anticipate nearly perfectly how cells would behave. Real mazes were built to the specifications optimized by the models. The purple colour shows an attractive chemical. Initially it’s everywhere, but the cells break it down. As new chemical diffuses in from the surroundings a gradient is set up, and the cells read that gradient (which they created themselves) to see where they should go. Credit: Luke Tweedy, Michele Zagnoni, Cancer Research UKReal amoebas (Dictyostelium discoideum cells) solving mazes of different shapes (simple maze). Remarkably, the cells can anticipate the correct turn before they reach it, especially in the simple maze. Credit: Luke Tweedy, Michele Zagnoni, Cancer Research UKReal amoebas (Dictyostelium discoideum cells) solving mazes of different shapes (complex maze). Remarkably, the cells can anticipate the correct turn before they reach it, especially in the simple maze. Credit: Luke Tweedy, Michele Zagnoni, Cancer Research UKCancer cells (pancreatic cancer - pancreatic ductal adenocarcinoma, grown in culture) solving mazes of different shapes (simple maze). They are less perfect than the amoebas, but still scarily accurate. Credit: Luke Tweedy, Michele Zagnoni, Cancer Research UKCancer cells (pancreatic cancer - pancreatic ductal adenocarcinoma, grown in culture) solving mazes of different shapes (complex maze). They are less perfect than the amoebas, but still scarily accurate. Credit: Luke Tweedy, Michele Zagnoni, Cancer Research UKMazes that are easy and difficult for cells to navigate. What is easy for cells is not the same as for humans – cells are confused by long correct paths and branched incorrect paths. This video shows real microfluidic devices. Credit: Luke Tweedy, Michele Zagnoni, Cancer Research UKMazes that are easy and difficult for cells to navigate. What is easy for cells is not the same as for humans – cells are confused by long correct paths and branched incorrect paths. This video shows simulations. Credit: Luke Tweedy, Michele Zagnoni, Cancer Research UKThe team designed a version of the famous Hampton Court palace maze and built it in microscale (the paths are less than 50 microns wide). Cells are easily able to solve it (better than people, in fact). The team also noticed an imperfection in the microfluidic device that caused a small short circuit; cells easily noticed it and took advantage of a shorter route. Credit: Luke Tweedy, Michele Zagnoni, Cancer Research UKThe team deliberately introduced a major short circuit to the Hampton Court palace maze. Many cells detect it easily and take the shortest route. The ones that take the short route confuse the others and stop them reaching the end. Credit: Luke Tweedy, Michele Zagnoni, Cancer Research UK
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How cells can find their way through the human body (2020, August 28)
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