Collective migration and cell jamming.

Our traditional physical picture holds with the intuitive notion that each individual cell comprising the cellular collective senses signals or gradients and then mobilizes physical forces in response. Those forces, in turn, drive local cellular motions from which collective cellular migrations emerge. Although it does not account for spontaneous noisy fluctuations that can be quite large, the tacit assumption has been one of linear causality in which systematic local motions, on average, are the shadow of local forces, and these local forces are the shadow of the local signals. New lines of evidence now suggest a rather different physical picture in which dominant mechanical events may not be local, the cascade of mechanical causality may be not so linear, and, surprisingly, the fluctuations may not be noise as much as they are an essential feature of mechanism. Here we argue for a novel synthesis in which fluctuations and non-local cooperative events that typify the cellular collective might be illuminated by the unifying concept of cell jamming. Jamming has the potential to pull together diverse factors that are already known to contribute but previously had been considered for the most part as acting separately and independently. These include cellular crowding, intercellular force transmission, cadherin-dependent cell-cell adhesion, integrin-dependent cell-substrate adhesion, myosin-dependent motile force and contractility, actin-dependent deformability, proliferation, compression and stretch.