Anomalous transport in the crowded world of biological cells

A ubiquitous observation in cell biology is that diffusion of macromolecules and organelles is anomalous, and a description simply based on the conventional diffusion equation with diffusion constants measured in dilute solution fails. This is commonly attributed to macromolecular crowding in the interior of cells and in cellular membranes, summarising their densely packed and heterogeneous structures. The most familiar phenomenon is a power-law increase of the MSD, but there are other manifestations like strongly reduced and time-dependent diffusion coefficients, persistent correlations, non-gaussian distributions of the displacements, heterogeneous diffusion, and immobile particles. After a general introduction to the statistical description of slow, anomalous transport, we summarise some widely used theoretical models: gaussian models like FBM and Langevin equations for visco-elastic media, the CTRW model, and the Lorentz model describing obstructed transport in a heterogeneous environment. Emphasis is put on the spatio-temporal properties of the transport in terms of 2-point correlation functions, dynamic scaling behaviour, and how the models are distinguished by their propagators even for identical MSDs. Then, we review the theory underlying common experimental techniques in the presence of anomalous transport: single-particle tracking, FCS, and FRAP. We report on the large body of recent experimental evidence for anomalous transport in crowded biological media: in cyto- and nucleoplasm as well as in cellular membranes, complemented by in vitro experiments where model systems mimic physiological crowding conditions. Finally, computer simulations play an important role in testing the theoretical models and corroborating the experimental findings. The review is completed by a synthesis of the theoretical and experimental progress identifying open questions for future investigation.Comment: review article, to appear in Rep. Prog. Phy

How Glassy Relaxation Slows Down by Increasing Mobility

We investigate how structural relaxation in mixtures with strong dynamical asymmetry is affected by the microscopic dynamics. Brownian and Newtonian dynamics simulations of dense mixtures of fast and slow hard spheres reveal a striking trend reversal. Below a critical density, increasing the mobility of the fast particles fluidizes the system, yet, above that critical density, the same increase in mobility strongly hinders the relaxation of the slow particles. The critical density itself does not depend on the dynamical asymmetry and can be identified with the glass-transition density of the mode-coupling theory. The asymptotic dynamics close to the critical density is universal, but strong pre-asymptotic effects prevail in mixtures with additional size asymmetry. This observation reconciles earlier findings of a strong dependence on kinetic parameters of glassy dynamics in colloid--polymer mixtures with the paradigm that the glass transition is determined by the properties of configuration space alone