Anomalous Diffusion on the Surface of Mammalian Cells

Tracking individual proteins on the surface of live mammalian cells reveals complex dynamics involving anomalous diffusion and clustering into nanoscale domains. Theoretical models indicate that anomalous diffusion can be caused by vastly different processes. By performing time series and ensemble analysis of extensive single-molecule tracking in combination with stochastic modeling, we show that most trajectories violate the ergodic hypothesis, one of the cornerstones of statistical physics. In particular, ergodicity breaking manifests as substantial differences between the time-averaged and the ensemble-averaged observables. We find that ergodicity breaking is caused by the transient localization of membrane proteins within nanoscale domains, such as endocytic pits and protein clusters. Furthermore, using a combination of dynamic super-resolution imaging and single-particle tracking, we observe that the actin cytoskeleton introduces barriers leading to the compartmentalization of the plasma membrane and that proteins are transiently confined within actin-delimited domains. Our results show that the actin-induced compartments are scale free and that the actin cortex forms a self-similar fractal structure.