Invisible to us, the cells in our tissues and organs – trillions of them – are constantly on the move. In fact, the ability of cells to get where they need to go is essential to our health and survival. Skin cells migrate to heal wounds. Immune system cells migrate to fight infections. “Every day, you look at your body and it’s not changing much,” said Peter Devreotes, a professor of cell biology at the Johns Hopkins University School of Medicine. “But the cells within it are migrating constantly.”
It starts from the earliest stages of life. When we are embryos just a few weeks old, a special group of “neural crest” cells in our back suddenly spreads through the body to become a wide range of essential tissues — bones, cartilage and nerves in the face, tendons, pigment cells in the skin, parts of the heart and more.
But how do these cells know where to go? Studies long suggested that they were following chemical trails to their routes. Like dogs trotting toward the scent of food, the cells sensed the gradient and followed the stream of signals back to the source. Yet scientists suspected that this system can’t sustain many of the migrations that unfold in the body. The structure of simple passive gradients is too fragile and too easily disrupted. New work shows that in addition to using chemical cues, neural crest cells “feel” their way through the body, creating patterns of physical tension in the surrounding tissue that point them the right way. In effect, the cells create the signals or self-generated gradients that they use to steer themselves.Cells even use their self-generated gradients to solve complicated mazes, including a miniature imitation of the famous trapezoidal hedge maze that King William III built at Hampton Court in England. In a recent lab experiment, Dr. Robert Insall and his colleagues at the University of Glasgow built a miniature replica of the hedge maze at Hampton Court Palace in England, and found that social slime-mold amoebas (Dictyostelium discoideum) solved it efficiently, as seen in the following time-lapse video which shows that chemical gradients created by the cells that led the way discouraged the cells behind them from going down dead ends.
That these cellular self-generated gradients work so well and are so impressively resilient to disruptions has spurred further research into their amazing properties. Recent research led by Sujit Datta, an assistant professor of chemical and biological engineering at Princeton University, has illustrated just how robust self-generated gradients can be. Datta’s team 3D-printed squiggles of E. coli (a gut bacteria commonly found in warm-blooded animals), into gels — “basically like ball pits for cells,” he said. No matter how squiggly the lines were, the migrating cells always smoothed out into an even band as they spread outward into the gel, suggesting that they help to smooth out important processes in development and healing so that they are not easily thrown off by disruptions.
The new discoveries show that groups of cells are less like soldiers following precise orders and more like soccer players. When the ball comes to them, they make snap decisions and adapt to changing surroundings. “We’re realizing that there’s a lot more control at the level of the cells,” says Darren Gilmour, a professor of molecular life sciences at Zurich University. “And they make the decisions together.”
Self-generated gradients have now made sense of perplexing behavior in cancer cells, fish embryos, immune cells, bacteria, slime mold, and more — and findings are accumulating rapidly. There will surely be more surprises ahead.