Cell Groups Push, not Pull, Themselves into Place

Research led by NYU Grossman School of Medicine and the NYU Courant Institute of Mathematical Sciences has found that cells push on surrounding tissue to move in groups as they form organs in an embryo, track down invading bacteria, or become cancerous and spread. The findings, published Nature Cell Biology, run contrary to previous culture studies that suggested cells pulled themselves forward with their front edges.

Using advanced microscopy, the study examined cell group motion in a zebrafish embryo, where external embryo development enabled the researchers to track movement of the primordium as it migrated from behind the ear to the tip of the zebrafish tail. There, the primordium cells mature into an organ that senses water flow.

The study used a new technique to measure the forces applied by a cell group as it moved along a “road-like” tissue membrane and into place. The study found, for the first time in an animal tissue, that proteins called integrins on the surfaces of the cells at the rear attach in greater numbers to the membrane as they move along, and exert more force in one direction, than the cells in the group’s front. The integrin clusters observed in the embryo were smaller than those seen in culture studies, and broke down faster.

Using “bleached” dots on the basement membrane to measure deformations on a minute scale, and a new software called embryogram to calculate how far the dots move as the primordium “grips” the membrane, the researchers determined how much the cells pulled and pushed on the membrane. Interestingly, they found that the primordium moved in a “continuous breaststroke” by pushing the basement membrane downward, sideways and backwards, much like the arms of a swimmer. The authors do not know why this is, but speculate that this is the most efficient way to move forward.

“Our results clarify how cell groups that will become organs move into place, and reaffirm that cells behave differently when removed from their natural environments,” said senior study author Holger Knaut, PhD, associate professor in the Department of Cell Biology at NYU Langone Health.

The findings may also have implications in oncology, as many cancers spread in cell groups and may use this “rear engine propulsion” mechanism.  This knowledge could be harnessed to stop cancer spread by designing treatments that block the action of integrins. Integrin inhibitors have been tested as drugs for cardiovascular and autoimmune disease in clinical trials, but their use against cancer spread has been limited by the need for a better understanding of the mechanisms.