Identifying heterogeneous diffusion states in the cytoplasm by a hidden Markov model

Diffusion of nanoparticles in the cytoplasm of live cells has frequently been reported to exhibit an anomalous and even heterogeneous character, i.e. particles seem to switch gears during their journey. Here we show by means of a hidden Markov model that individual trajectories of quantum dots in the cytoplasm of living cultured cells feature a dichotomous switching between two distinct mobility states with an overall subdiffusive mode of motion of the fractional Brownian motion (FBM) type. Using the extracted features of experimental trajectories as input for simulations of different variants of a two-state FBM model, we show that the trajectory-intrinsic and the ensemble-wise heterogeneity in the experimental data is mostly due to variations in the (local) transport coefficients, with only minor contributions due to locally varying anomaly exponents. Altogether, our approach shows that diffusion heterogeneities can be faithfully extracted and quantified from fairly short trajectories obtained by single-particle tracking in highly complex media.