Felix Höfling

Anomalous transport in the crowded world of biological cells

A ubiquitous observation in cell biology is that the diffusive motion 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, summarizing their densely packed and heterogeneous structures. The most familiar phenomenon is a sublinear, power-law increase of the mean-square displacement (MSD) as a function of the lag time, but there are other manifestations like strongly reduced and time-dependent diffusion coefficients, persistent correlations in time, non-Gaussian distributions of spatial displacements, heterogeneous diffusion and a fraction of immobile particles. After a general introduction to the statistical description of slow, anomalous transport, we summarize some widely used theoretical models: Gaussian models like fractional Brownian motion and Langevin equations for visco-elastic media, the continuous-time random walk model, and the Lorentz model describing obstructed transport in a heterogeneous environment. Particular emphasis is put on the spatio-temporal properties of the transport in terms of two-point correlation functions, dynamic scaling behaviour, and how the models are distinguished by their propagators even if the MSDs are identical. Then, we review the theory underlying commonly applied experimental techniques in the presence of anomalous transport like single-particle tracking, fluorescence correlation spectroscopy (FCS) and fluorescence recovery after photobleaching (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 a variety of model systems mimic physiological crowding conditions. Finally, computer simulations are discussed which 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.

Localization transition of the three-dimensional lorentz model and continuum percolation.

The localization transition and the critical properties of the Lorentz model in three dimensions are investigated by computer simulations. We give a coherent and quantitative explanation of the dynamics in terms of continuum percolation theory and obtain an excellent matching of the critical density and exponents. Within a dynamic scaling ansatz incorporating two divergent length scales we achieve data collapse for the mean-square displacements and identify the leading corrections to scaling. We provide evidence for a divergent non-Gaussian parameter close to the transition.

Phase transition and critical behavior of the d=3 Gross-Neveu model

A second-order phase transition for the three-dimensional Gross-Neveu model is established for one fermion species, N=1. This transition breaks a paritylike discrete symmetry. It constitutes its peculiar universality class with critical exponent v=0.63 and scalar and fermionic anomalous dimensions η s =0.31 and η ] =0.11, respectively. We also compute critical exponents for other N. Our results are based on exact renormalization-group equations.

Highly accelerated simulations of glassy dynamics using GPUs: Caveats on limited floating-point precision

Modern graphics processing units (GPUs) provide impressive computing resources, which can be accessed conveniently through the CUDA programming interface. We describe how GPUs can be used to considerably speed up molecular dynamics (MD) simulations for system sizes ranging up to about 1 million particles. Particular emphasis is put on the numerical long-time stability in terms of energy and momentum conservation, and caveats on limited floating-point precision are issued. Strict energy conservation over 108 MD steps is obtained by double-single emulation of the floating-point arithmetic in accuracy-critical parts of the algorithm. For the slow dynamics of a supercooled binary Lennard-Jones mixture, we demonstrate that the use of single-floating point precision may result in quantitatively and even physically wrong results. For simulations of a Lennard-Jones fluid, the described implementation shows speedup factors of up to 80 compared to a serial implementation for the CPU, and a single GPU was found to compare with a parallelised MD simulation using 64 distributed cores.

Crossover in the slow decay of dynamic correlations in the lorentz model.

The long-time behavior of transport coefficients in a model for spatially heterogeneous media in two and three dimensions is investigated by molecular dynamics simulations. The behavior of the velocity autocorrelation function is rationalized in terms of a competition of the critical relaxation due to the underlying percolation transition and the hydrodynamic power-law anomalies. In two dimensions and in the absence of a diffusive mode, another power-law anomaly due to trapping is found with an exponent -3 instead of -2. Further, the logarithmic divergence of the Burnett coefficient is corroborated in the dilute limit; at finite density, however, it is dominated by stronger divergences.

Critical dynamics of ballistic and Brownian particles in a heterogeneous environment

The dynamic properties of a classical tracer particle in a random, disordered medium are investigated close to the localization transition. For Lorentz models obeying Newtonian and diffusive motion at the microscale, we have performed large-scale computer simulations, demonstrating that universality holds at long times in the immediate vicinity of the transition. The scaling function describing the crossover from anomalous transport to diffusive motion is found to vary extremely slowly and spans at least five decades in time. To extract the scaling function, one has to allow for the leading universal corrections to scaling. Our findings suggest that apparent power laws with varying exponents generically occur and dominate experimentally accessible time windows as soon as the heterogeneities cover a decade in length scale. We extract the divergent length scales, quantify the spatial heterogeneities in terms of the non-Gaussian parameter, and corroborate our results by a thorough finite-size analysis.

Cluster-resolved dynamic scaling theory and universal corrections for transport on percolating systems

For percolating systems, we propose a universal exponent relation connecting the leading corrections to scaling of the cluster size distribution with the dynamic corrections to the asymptotic transport behaviour at criticality. Our derivation is based on a cluster-resolved scaling theory unifying the scaling of both the cluster size distribution and the dynamics of a random walker. We corroborate our theoretical approach by extensive simulations for a site percolating square lattice and numerically determine both the static and dynamic correction exponents.

Anomalous transport resolved in space and time by fluorescence correlation spectroscopy

A ubiquitous observation in crowded cell membranes is that molecular transport does not follow Fickian diffusion but exhibits subdiffusion. The microscopic origin of such a behaviour is not understood and highly debated. Here we discuss the spatio-temporal dynamics for two models of subdiffusion: fractional Brownian motion and hindered motion due to immobile obstacles. We show that the different microscopic mechanisms can be distinguished using fluorescence correlation spectroscopy (FCS) by systematic variation of the confocal detection area. We provide a theoretical framework for space-resolved FCS by generalising FCS theory beyond the common assumption of spatially Gaussian transport. We derive a master formula for the FCS autocorrelation function, from which it is evident that the beam waist of an FCS experiment is a similarly important parameter as the wavenumber of scattering experiments. These results lead to scaling properties of the FCS correlation for both models, which are tested by in silico experiments. Further, our scaling prediction is compatible with the FCS half-value times reported by Wawrezinieck et al. [Biophys. J., 2005, 89, 4029] for in vivo experiments on a transmembrane protein.

The localization transition of the two-dimensional Lorentz model

Abstract. We investigate the dynamics of a single tracer particle performing Brownian motion in a two-dimensional course of randomly distributed hard obstacles. At a certain critical obstacle density, the motion of the tracer becomes anomalous over many decades in time, which is rationalized in terms of an underlying percolation transition of the void space. In the vicinity of this critical density the dynamics follows the anomalous one up to a crossover time scale where the motion becomes either diffusive or localized. We analyze the scaling behavior of the time-dependent diffusion coefficient D(t) including corrections to scaling. Away from the critical density, D(t) exhibits universal hydrodynamic long-time tails both in the diffusive as well as in the localized phase.

Anomalous transport of a tracer on percolating clusters

We investigate the dynamics of a single tracer exploring a course of fixed obstacles in the vicinity of the percolation transition for particles confined to the infinite cluster. The mean-square displacement displays anomalous transport, which extends to infinite times precisely at the critical obstacle density. The slowing down of the diffusion coefficient exhibits power-law behavior for densities close to the critical point and we show that the mean-square displacement fulfills a scaling hypothesis. Furthermore, we calculate the dynamic conductivity as a response to an alternating electric field. Last, we discuss the non-gaussian parameter as an indicator for heterogeneous dynamics.