  Cell polarization and directional cell migration can display random,
persistent and oscillatory dynamic patterns. However, it is not clear if these
polarity patterns can be explained by the same underlying regulatory mechanism.
Here, we show that random, persistent and oscillatory migration accompanied by
polarization can simultaneously occur in populations of melanoma cells derived
from tumors with different degrees of aggressiveness. We demonstrate that all
these patterns and the probabilities of their occurrence are quantitatively
accounted for by a simple mechanism involving a spatially distributed,
mechano-chemical feedback coupling the dynamically changing extracellular
matrix (ECM)-cell contacts to the activation of signaling downstream of the
Rho-family small GTPases. This mechanism is supported by a predictive
mathematical model and extensive experimental validation, and can explain
previously reported results for diverse cell types. In melanoma, this mechanism
also accounts for the effects of genetic and environmental perturbations,
including mutations linked to invasive cell spread. The resulting mechanistic
understanding of cell polarity quantitatively captures the relationship between
population variability and phenotypic plasticity, with the potential to account
for a wide variety of cell migration states in diverse pathological and
physiological conditions.
