Backward waves move cells forward

dvancing cells periodically pull on their substrates to test the environment, say Grégory Giannone, Michael Sheetz (Columbia University, New York, NY), and colleagues. The actomyosin contractions both strengthen attachments to more solid substrates, and break off part of a signaling complex so that it can be carried into the cell. Once that retrograde signal reaches myosin, which is some distance from the cell edge, a new contraction is initiated. “This cements the idea that what the cell is doing with its actin machinery is testing its environment,” says Sheetz. And, he says, it provides a justification for why cells allow actin to flow backward, away from the cell front, even as they use forward protrusion of actin to drive cell movement. The key to the probing, and one reason that it took some time to spot, is that its periodicity is localized and not synchronized over the whole cell. Each part of the cell surface is advancing and contracting (i.e., stopping) on its own schedule, although the time between contractions is the same all over the cell (24 s for the cell type under study). The 24 s matches the time taken for signaling complexes— F-actin and associated -actinin and myosin light chain kinase (MLCK)—to traverse the protruding lamellipodia. The time increases or decreases after treatments that expand or shrink the lamellipodia. The contractions may be triggered by arrival of the myosinactivating MLCK at the base of the lamellipodium. Each periodic contraction then results in a row of transient integrin–paxillin A