Plithotaxis: how crowds of cells find their way

First measurements of forces driving collective cell migration unveil new principle in biology

Processes like tissue regeneration and cancer metastasis rely on groups of cells moving long distances without losing their cohesiveness, but how they do this has remained unknown. Now researchers from the Institute for Bioengineering of Catalonia (IBEC) and Harvard University have solved the mystery and unveiled a brand new phenomenon in biology.

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In the journal Nature Materials today, the scientists describe their newly discovered principle, plithotaxis, in which migrating cells pull on each other in a very disordered yet effective manner to reach their common goal: the movement of the crowd as a whole. “Our findings show that each cell in a group performs a wild and chaotic dance of its own that, while appearing random, contributes to the intended direction of the movement and is innately collective,” explains IBEC researcher Xavier Trepat.

Xavier and his collaborators in the United States, Dhananjay Tambe, C. Corey Hardin and Jeffrey Fredberg, used a method they developed called Monolayer Stress Microscopy (MSM) to look at the mechanical forces exerted at cell-cell junctions in migrating groups. “Newton taught us that the motion of any object cannot be understood except in the context of forces,” explains Xavier. “Cells are no exception.”

Using MSM the researchers were able to map these forces for the first time, revealing an unanticipated and novel principle. “Rather than showing smooth, systematic variation within moving group, the distribution of physical forces is very rugged: fluctuating abruptly in time and space, emerging spontaneously, and cooperating across many cell bodies,” says Xavier, who’s also a professor at the University of Barcelona’s Faculty of Medicine. “This shows that there’s more happening than just the well-known mechanisms of chemotaxis, durotaxis or haptotaxis, for example, where cells respond to signals or follow gradients.”

The name plithotaxis comes from plithos, which means crowd, swarm, or throng in Greek, and captures the dynamic heterogeneities and intercellular cooperativity of this new mechanism of cell guidance in collective cell migration. “The discovery of a relationship between physical forces and individual cellular motions in vitro means that further tests are needed to see whether it holds in in vivo tissues, and could open new avenues in predicting the movement of cancer cells,” says Xavier.

The findings also show that understanding each constituent cell within a moving group will never be sufficient to understand the group’s overall behaviour.  “Just as with flocks of migrating birds, most details about the biology of the bird are irrelevant to understand its group behaviour; what really matters is how each one interacts with its neighbours,” says Xavier. “This might be the most important thing we learned in this study. Rather than trying to understand every nanoscale detail of every single cell, we should perhaps focus our efforts in understanding how each influences the others. Unlike the case of birds migrating, cells pull directly on each other, so we need a great deal of physics to understand their interaction.”

 

Source: Tambe et al (2011). Collective cell guidance by cooperative intercellular forces. Nature Materials

>> IBEC in the Media: News-Medical.net: “Scientists invent Monolayer Stress Microscopy to measure physical forces during collective cellular migration