Stochastic motion on the surface of living cells is critical to promote molecular encounters that are necessary for multiple cellular processes. Often the complexity of the cell membranes leads to anomalous diffusion, which under certain conditions it is accompanied by non-ergodic dynamics. Here, we unravel two manifestations of ergodicity breaking in the dynamics of membrane proteins in the somatic surface of hippocampal neurons. Three different tagged molecules are studied on the surface of the soma: the voltage-gated potassium and sodium channels Kv1.4 and Nav1.6 and the glycoprotein CD4. In these three molecules ergodicity breaking is unveiled by the confidence interval of the mean square displacement and by the dynamical functional estimator. Ergodicity breaking is found to take place due to transient confinement effects since the molecules alternate between free diffusion and confined motion.

Fractional Brownian motion, a Gaussian non-Markovian self-similar process with stationary long-correlated increments, has been identified to give rise to the anomalous diffusion behavior in a great variety of physical systems. The correlation and diffusion properties of this random motion are fully characterized by its index of self-similarity or the Hurst exponent. However, recent single-particle tracking experiments in biological cells revealed highly complicated anomalous diffusion phenomena that cannot be attributed to a class of self-similar random processes. Inspired by these observations, we here study the process that preserves the properties of the fractional Brownian motion at a single trajectory level; however, the Hurst index randomly changes from trajectory to trajectory. We provide a general mathematical framework for analytical, numerical, and statistical analysis of the fractional Brownian motion with the random Hurst exponent. The explicit formulas for probability density function, mean-squared displacement, and autocovariance function of the increments are presented for three generic distributions of the Hurst exponent, namely, two-point, uniform, and beta distributions. The important features of the process studied here are accelerating diffusion and persistence transition, which we demonstrate analytically and numerically.

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.

We propose a generalization of the widely used fractional Brownian motion (FBM), memory-multi-FBM (MMFBM), to describe viscoelastic or persistent anomalous diffusion with time-dependent memory exponent $\alpha \left(t\right)$ in a changing environment. In MMFBM the built-in, long-range memory is continuously modulated by $\alpha \left(t\right)$. We derive the essential statistical properties of MMFBM such as its response function, mean-squared displacement (MSD), autocovariance function, and Gaussian distribution. In contrast to existing forms of FBM with time-varying memory exponents but a reset memory structure, the instantaneous dynamic of MMFBM is influenced by the process history, e.g., we show that after a steplike change of $\alpha \left(t\right)$ the scaling exponent of the MSD after the $\alpha$ step may be determined by the value of $\alpha \left(t\right)$ before the change. MMFBM is a versatile and useful process for correlated physical systems with nonequilibrium initial conditions in a changing environment.

The stochastic trajectories of molecules in living cells, as well as the dynamics in many other complex systems, often exhibit memory in their path over long periods of time. In addition, these systems can show dynamic heterogeneities due to which the motion changes along the trajectories. Such effects manifest themselves as spatiotemporal correlations. Despite the broad occurrence of heterogeneous complex systems in nature, their analysis is still quite poorly understood and tools to model them are largely missing. We contribute to tackling this problem by employing an integral representation of Mandelbrot’s fractional Brownian motion that is compliant with varying motion parameters while maintaining long memory. Two types of switching fractional Brownian motion are analysed, with transitions arising from a Markovian stochastic process and scale-free intermittent processes. We obtain simple formulas for classical statistics of the processes, namely the mean squared displacement and the power spectral density. Further, a method to identify switching fractional Brownian motion based on the distribution of displacements is described. A validation of the model is given for experimental measurements of the motion of quantum dots in the cytoplasm of live mammalian cells that were obtained by single-particle tracking.

The Langevin equation is a common tool to model diffusion at a single-particle level. In nonhomogeneous environments, such as aqueous two-phase systems or biological condensates with different diffusion coefficients in different phases, the solution to a Langevin equation is not unique unless the interpretation of stochastic integrals involved is selected. We analyze the diffusion of particles in such systems and evaluate the mean, the mean square displacement, and the distribution of particles, as well as the variance of the time-averaged mean-square displacements. Our analytical results provide a method to choose the interpretation parameter from single-particle tracking experiments.