Smart bombs keep the cell moving.

Case closed, at least for fish skin. In fibroblasts Mitchison and Louise Cramer of University College, London, think that myosin may drag the nucleus forward on large, established roadways of actin, although Borisy says no one has shown that those roadways are relevant to movement.

But neither Borisy nor Cramer claim that two proteins are enough for all cells. Larger cells need something more, and, like actin and myosin, that something must be capable of recreating itself as the cell moves forwards.

For the sluggish fibroblasts, the extra ingredient is a set of train tracks called microtubules – thin tubes that radiate from the front of the nucleus like the rays of the sun. Microtubule tracks are known as highways for delivering building materials, so it had been presumed that they were fulfilling the same function at the front of moving cells. But fibroblasts, when they are poisoned with anti-cancer drugs that eliminate microtubules, seem to be lacking not bricks and mortar but organization. "They attempt to go in all directions simultaneously," says Borisy. "The rationalization is that with a large cell you need some way to control all the pieces," so perhaps the microtubules are the master conductor that defines front and back. "That’s very far from molecules or mechanisms, but that’s where the field is," says Borisy. "It’s a frontier area."

Microtubules as smart bombs.

The first clue as to how microtubules work came in May 1999 from Ted Salmon of the University of North Carolina at Chapel Hill. He found that microtubules deliver a signal that makes the front of the cell poke out and then attach. But then Victor Small of the Austrian Academy of Sciences in Salzburg reported a contradictory ungluing effect of microtubules in a September 1999 article. Small watched microtubules as they lengthened and shortened, and found that they were acting like smart bombs. An extraordinary number of them were lured exactly to the sites where actin cables are anchored to the surface underlying the cell. Sites at the back of the cell were targeted eight times more frequently than those at the front, and arrival of a microtubule was often followed soon after by disappearance of the anchor.

The adhesion-dissolving may be needed to compensate for the fibroblasts’ indecision. "The contacts at the back are mostly formed when the cell was thinking of going in that direction but then changed its mind," says Small. The microtubules should help the back to unstick itself and keep moving forwards.

Making a Movement Machine