  A living cell's interior is one of the most complex and intrinsically dynamic
systems, providing an elaborate interplay between cytosolic crowding and
ATP-driven motion, which controls cellular functionality. Here, we investigated
two distinct fundamental features of the merely passive, not-bio-motor shuttled
material transport within the cytoplasm of Dictyostelium discoideum cells: the
anomalous non-linear scaling of the mean-squared displacement of a
150nm-diameter particle and non-Gaussian distribution of increments. Relying on
single-particle tracking data of 320,000 data points, we performed a systematic
analysis of four possible origins for non-Gaussian transport: (1) sample-based
variability, (2) rare occurring strong motion events, (3) ergodicity
breaking/ageing, and (4) spatio-temporal heterogeneities of the intracellular
medium. After excluding the first three reasons, we investigated the remaining
hypothesis of a heterogeneous cytoplasm as cause for non-Gaussian transport. A
novel fit model with randomly distributed diffusivities implementing medium
heterogeneities suits the experimental data. Strikingly, the non-Gaussian
feature is independent of the cytoskeleton condition and lag time. This reveals
that efficiency and consistency of passive intracellular transport and the
related anomalous scaling of the mean-squared displacement are regulated by
cytoskeleton components, while cytoplasmic heterogeneities are responsible for
the generic, non-Gaussian distribution of increments.
