The physical forces that guide how cells migrate--how they manage to get from place to place in a coordinated fashion inside the living body-- are poorly understood. Our group devised, for the first time, a technique to measure these forces during collective cellular migration. Using this technique we reached the surprising conclusion that the cells fight it out, each pushing and pulling on its neighbors in a chaotic dance, yet together moving cooperatively toward their intended direction.
Until now it was known that cells could follow gradients of soluble chemical cues, called morphogens, which help to direct tissue development, or they could follow physical cues, such as adhesion to their surroundings. Fundamental studies of these and other mechanisms of cellular migration have focused on dissecting cell behavior into ever smaller increments, trying to get to the molecular roots of how migration occurs. In contrast, we decided to work at a higher level--the group level--and focused on the forces that cells exert upon their immediate neighbors.
Collective cellular migrations are necessary for multicellular life; for example, in order for cells to form the embryo, cells must move collectively. Or in the healing of a wound, cells must migrate collectively to fill the wound gap. But the migration process is also dangerous in situations such as cancer, when malignant cells, or clumps of cells, can migrate to distant sites to invade other tissues or form new tumors. Understanding how and why collective cellular migration happens may lead to ways to control or interrupt diseases that involve abnormal cell migration. To this aim, we developped a measurement technology called Monolayer Stress Microscopy, which allows us to visualize the nanoscale mechanical forces exerted at the junctions where individual cells are connected.
We initially thought that as cells are moving--say, to close a wound--the underlying forces would be synchronized and smoothly changing so as to vary coherently across the crowd of cells, as in a minuet. Instead, we found the forces to vary tremendously, occurring in huge peaks and valleys across the monolayer. So the forces are not smooth and orderly at all; they are more like those in a `mosh pit'--organized chaos with pushing and pulling in all directions at once, but collectively giving rise to motion in a given direction. We named this new phenomenon "plithotaxis," a term derived from Greek "plithos" suggestive of throng, swarm or crowd.