On the trail of cell navigation

Secreted molecules might help steer cellular migrations, simulation shows

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Cells seeking paths through the body’s tangle of tissues might adapt the navigational strategy of Hansel and Gretel. In the Brothers Grimm tale, the lost kids dropped pebbles and bread crumbs along a wooded trail to help lead them back out of a freaky forest.

Instead of using markers telling them where to go, though, cells might leave behind repellent molecules telling them where not to go.

In a new study, scientists suggest these markers help trailblazing cells move away from areas where they’ve gotten stuck, such as confusing dead ends and tricky corners.

“I think it’s a really nice idea that cells could be using something like this, a simple mechanism that allows them to navigate through these complex environments,” says biologist Iain Couzin of Princeton University, who was not involved in the study.

Moving through complex environments is a challenge faced by many cells — traveling cancer cells, infection-bound immune cells, or neurons moving through the brain, for example. Scientists know that cell travel is directed, in part, by a chemical gradient — spatial differences in chemical concentrations — that helps the cells move in the right direction.

But the gradient alone isn’t enough to explain successful cell navigation in complex situations, says physicist Inbal Hecht of Tel Aviv University in Israel, who coauthored the study appearing August 4 in PLoS ONE. “If this were the case, we wouldn’t see such a great success in navigating,” Hecht says.

So, she and her colleagues tested whether cells might employ a form of navigational memory in their treks — the self-secreted repellent molecules. The researchers used a simulated gradient and a wandering, computerized version of the amoeba Dictyostelium, chosen because its movement mechanics are well-understood. The team had the amoeba find its way from one end of the computerized chemical gradient to the other and put increasingly difficult obstacles in its way, including a maze.

“The simulated cells are extremely impressive, extremely life-like,” Couzin says. “They capture the key principles that one sees in real cells. This is a very biologically motivated experiment.”

On its own, the computerized amoeba made it through the maze only 30 percent of the time. When it had the ability to secrete repellent markers, the amoeba’s success rate rose to 99 percent.

“This is really a proof of principle,” says physicist and coauthor Eshel Ben-Jacob of Tel Aviv University. Real cells probably use more complex strategies to help them move along and are much more efficient, he says.

The team is testing real cells’ navigational abilities using breast cancer cells and a maze that fits in a petri dish. “The breast matrix is very complex,” Ben-Jacob says of the tissue’s structure. “The cells have to look for paths. It’s very much like moving in a maze.”

The researchers hope that understanding how cells navigate will provide a new means of thwarting cancer cells. We might be able to suppress their ability to move,” Hecht says, “or inject some kind of a chemical that will confuse them, and keep them where they are.”

Simulated amoeba navigating without markers

Simulated amoeba navigating with markers

Simulations show an amoeba’s movement through a maze. In the left video, the computerized amoeba is using only differences in the chemical gradient (indicated by colors) to find its way. In the right video, the amoeba is leaving faint repellent markers along its way.
CREDIT: I. Hecht