Waves of contraction (blue) slow down forward movement but allow adhesion.


Advancing 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 α-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 myosin-activating MLCK at the base of the lamellipodium. Each periodic contraction then results in a row of transient integrin–paxillin clusters being laid down near the cell front. Formation of these links to the extracellular matrix, and thus the occurrence of effective protrusion, is only supported by rigid substrates. This requirement for rigidity may reflect the matrix dependence that keeps nontransformed cells from growing in places where they are not wanted.

The contractions are needed to test the environment, but they must be periodic so that the cell doesn't spend its whole time going backward. The periodicity is enforced by the distance traveled by the contraction signal. And directionality of the signal is maintained in transit by restricting the signal to travel along actin filaments. Similar direction-conserving signaling may operate in growth cones of neurons. ▪


Giannone, G., et al.