TY - JOUR A1 - Palyulin, Vladimir V. A1 - Metzler, Ralf T1 - Speeding up the first-passage for subdiffusion by introducing a finite potential barrier JF - Journal of physics : A, Mathematical and theoretical N2 - We show that for a subdiffusive continuous time random walk with scale-free waiting time distribution the first-passage dynamics on a finite interval can be optimized by introduction of a piecewise linear potential barrier. Analytical results for the survival probability and first-passage density based on the fractional Fokker-Planck equation are shown to agree well with Monte Carlo simulations results. As an application we discuss an improved design for efficient translocation of gradient copolymers compared to homopolymer translocation in a quasi-equilibrium approximation. KW - first passage KW - anomalous diffusion KW - potential landscape KW - polymer translocation Y1 - 2014 U6 - https://doi.org/10.1088/1751-8113/47/3/032002 SN - 1751-8113 SN - 1751-8121 VL - 47 IS - 3 PB - IOP Publ. Ltd. CY - Bristol ER - TY - JOUR A1 - Sanders, Lloyd P. A1 - Lomholt, Michael A. A1 - Lizana, Ludvig A1 - Fogelmark, Karl A1 - Metzler, Ralf A1 - Ambjoernsson, Tobias T1 - Severe slowing-down and universality of the dynamics in disordered interacting many-body systems: ageing and ultraslow diffusion JF - New journal of physics : the open-access journal for physics N2 - Low-dimensional, many-body systems are often characterized by ultraslow dynamics. We study a labelled particle in a generic system of identical particles with hard-core interactions in a strongly disordered environment. The disorder is manifested through intermittent motion with scale-free sticking times at the single particle level. While for a non-interacting particle we find anomalous diffusion of the power-law form < x(2)(t)> similar or equal to t(alpha) of the mean squared displacement with 0 < alpha < 1, we demonstrate here that the combination of the disordered environment with the many-body interactions leads to an ultraslow, logarithmic dynamics < x(2)(t)> similar or equal to log(1/2)t with a universal 1/2 exponent. Even when a characteristic sticking time exists but the fluctuations of sticking times diverge we observe the mean squared displacement < x(2)(t)> similar or equal to t(gamma) with 0 < gamma < 1/2, that is slower than the famed Harris law < x(2)(t)> similar or equal to t(1/2) without disorder. We rationalize the results in terms of a subordination to a counting process, in which each transition is dominated by the forward waiting time of an ageing continuous time process. KW - single-file diffusion KW - continuous time random walks KW - ageing Y1 - 2014 U6 - https://doi.org/10.1088/1367-2630/16/11/113050 SN - 1367-2630 VL - 16 PB - IOP Publ. Ltd. CY - Bristol ER - TY - JOUR A1 - Metzler, Ralf A1 - Sanders, L. A1 - Lomholt, M. A. A1 - Lizana, L. A1 - Fogelmark, K. A1 - Ambjoernsson, Tobias T1 - Ageing single file motion JF - The European physical journal Y1 - 2014 U6 - https://doi.org/10.1140/epjst/e2014-02333-5 SN - 1951-6355 SN - 1951-6401 VL - 223 IS - 14 SP - 3287 EP - 3293 PB - Springer CY - Heidelberg ER - TY - JOUR A1 - Cherstvy, Andrey G. A1 - Metzler, Ralf T1 - Nonergodicity, fluctuations, and criticality in heterogeneous diffusion processes JF - Physical review : E, Statistical, nonlinear and soft matter physics N2 - We study the stochastic behavior of heterogeneous diffusion processes with the power-law dependence D(x) similar to vertical bar x vertical bar(alpha) of the generalized diffusion coefficient encompassing sub- and superdiffusive anomalous diffusion. Based on statistical measures such as the amplitude scatter of the time-averaged mean-squared displacement of individual realizations, the ergodicity breaking and non-Gaussianity parameters, as well as the probability density function P(x, t), we analyze the weakly nonergodic character of the heterogeneous diffusion process and, particularly, the degree of irreproducibility of individual realizations. As we show, the fluctuations between individual realizations increase with growing modulus vertical bar alpha vertical bar of the scaling exponent. The fluctuations appear to diverge when the critical value alpha = 2 is approached, while for even larger alpha the fluctuations decrease, again. At criticality, the power-law behavior of the mean-squared displacement changes to an exponentially fast growth, and the fluctuations of the time-averaged mean-squared displacement do not converge for increasing number of realizations. From a systematic comparison we observe some striking similarities of the heterogeneous diffusion process with the familiar subdiffusive continuous time random walk process with power-law waiting time distribution and diverging characteristic waiting time. Y1 - 2014 U6 - https://doi.org/10.1103/PhysRevE.90.012134 SN - 1539-3755 SN - 1550-2376 VL - 90 IS - 1 PB - American Physical Society CY - College Park ER - TY - JOUR A1 - Goychuk, Igor A1 - Kharchenko, Vasyl O. A1 - Metzler, Ralf T1 - How Molecular Motors Work in the Crowded Environment of Living Cells: Coexistence and Efficiency of Normal and Anomalous Transport JF - PLoS one N2 - Recent experiments reveal both passive subdiffusion of various nanoparticles and anomalous active transport of such particles by molecular motors in the molecularly crowded environment of living biological cells. Passive and active microrheology reveals that the origin of this anomalous dynamics is due to the viscoelasticity of the intracellular fluid. How do molecular motors perform in such a highly viscous, dissipative environment? Can we explain the observed co-existence of the anomalous transport of relatively large particles of 100 to 500 nm in size by kinesin motors with the normal transport of smaller particles by the same molecular motors? What is the efficiency of molecular motors in the anomalous transport regime? Here we answer these seemingly conflicting questions and consistently explain experimental findings in a generalization of the well-known continuous diffusion model for molecular motors with two conformational states in which viscoelastic effects are included. Y1 - 2014 U6 - https://doi.org/10.1371/journal.pone.0091700 SN - 1932-6203 VL - 9 IS - 3 PB - PLoS CY - San Fransisco ER - TY - JOUR A1 - Schulz, Johannes H. P. A1 - Barkai, Eli A1 - Metzler, Ralf T1 - Aging renewal theory and application to random walks JF - Physical review : X, Expanding access N2 - We discuss a renewal process in which successive events are separated by scale-free waiting time periods. Among other ubiquitous long-time properties, this process exhibits aging: events counted initially in a time interval [0, t] statistically strongly differ from those observed at later times [t(a,) t(a) + t]. The versatility of renewal theory is owed to its abstract formulation. Renewals can be interpreted as steps of a random walk, switching events in two-state models, domain crossings of a random motion, etc. In complex, disordered media, processes with scale-free waiting times play a particularly prominent role. We set up a unified analytical foundation for such anomalous dynamics by discussing in detail the distribution of the aging renewal process. We analyze its half-discrete, half-continuous nature and study its aging time evolution. These results are readily used to discuss a scale-free anomalous diffusion process, the continuous-time random walk. By this, we not only shed light on the profound origins of its characteristic features, such as weak ergodicity breaking, along the way, we also add an extended discussion on aging effects. In particular, we find that the aging behavior of time and ensemble averages is conceptually very distinct, but their time scaling is identical at high ages. Finally, we show how more complex motion models are readily constructed on the basis of aging renewal dynamics. Y1 - 2014 U6 - https://doi.org/10.1103/PhysRevX.4.011028 SN - 2160-3308 VL - 4 IS - 1 PB - American Physical Society CY - College Park ER - TY - JOUR A1 - Palyulin, Vladimir V. A1 - Chechkin, Aleksei V. A1 - Metzler, Ralf T1 - Levy flights do not always optimize random blind search for sparse targets JF - Proceedings of the National Academy of Sciences of the United States of America N2 - It is generally believed that random search processes based on scale-free, Levy stable jump length distributions (Levy flights) optimize the search for sparse targets. Here we show that this popular search advantage is less universal than commonly assumed. We study the efficiency of a minimalist search model based on Levy flights in the absence and presence of an external drift (underwater current, atmospheric wind, a preference of the walker owing to prior experience, or a general bias in an abstract search space) based on two different optimization criteria with respect to minimal search time and search reliability (cumulative arrival probability). Although Levy flights turn out to be efficient search processes when the target is far from the starting point, or when relative to the starting point the target is upstream, we show that for close targets and for downstream target positioning regular Brownian motion turns out to be the advantageous search strategy. Contrary to claims that Levy flights with a critical exponent alpha = 1 are optimal for the search of sparse targets in different settings, based on our optimization parameters the optimal a may range in the entire interval (1, 2) and especially include Brownian motion as the overall most efficient search strategy. KW - search optimization KW - stochastic processes KW - Levy foraging hypothesis Y1 - 2014 U6 - https://doi.org/10.1073/pnas.1320424111 SN - 0027-8424 VL - 111 IS - 8 SP - 2931 EP - 2936 PB - National Acad. of Sciences CY - Washington ER - TY - JOUR A1 - Talukder, Srijeeta A1 - Sen, Shrabani A1 - Chakraborti, Prantik A1 - Metzler, Ralf A1 - Banik, Suman K. A1 - Chaudhury, Pinaki T1 - Breathing dynamics based parameter sensitivity analysis of hetero-polymeric DNA JF - The journal of chemical physics : bridges a gap between journals of physics and journals of chemistr N2 - We study the parameter sensitivity of hetero-polymeric DNA within the purview of DNA breathing dynamics. The degree of correlation between the mean bubble size and the model parameters is estimated for this purpose for three different DNA sequences. The analysis leads us to a better understanding of the sequence dependent nature of the breathing dynamics of hetero-polymeric DNA. Out of the 14 model parameters for DNA stability in the statistical Poland-Scheraga approach, the hydrogen bond interaction epsilon(hb)(AT) for an AT base pair and the ring factor. turn out to be the most sensitive parameters. In addition, the stacking interaction epsilon(st)(TA-TA) for an TA-TA nearest neighbor pair of base-pairs is found to be the most sensitive one among all stacking interactions. Moreover, we also establish that the nature of stacking interaction has a deciding effect on the DNA breathing dynamics, not the number of times a particular stacking interaction appears in a sequence. We show that the sensitivity analysis can be used as an effective measure to guide a stochastic optimization technique to find the kinetic rate constants related to the dynamics as opposed to the case where the rate constants are measured using the conventional unbiased way of optimization. (c) 2014 AIP Publishing LLC. Y1 - 2014 U6 - https://doi.org/10.1063/1.4869112 SN - 0021-9606 SN - 1089-7690 VL - 140 IS - 12 PB - American Institute of Physics CY - Melville ER - TY - JOUR A1 - Shin, Jaeoh A1 - Cherstvy, Andrey G. A1 - Metzler, Ralf T1 - Mixing and segregation of ring polymers: spatial confinement and molecular crowding effects JF - New journal of physics : the open-access journal for physics N2 - During the life cycle of bacterial cells the non-mixing of the two ring-shaped daughter genomes is an important prerequisite for the cell division process. Mimicking the environments inside highly crowded biological cells, we study the dynamics and statistical behavior of two flexible ring polymers in the presence of cylindrical confinement and crowding molecules. From extensive computer simulations we determine the degree of ring-ring overlap and the number of inter-monomer contacts for varying volume fractions phi of crowders. We also examine the entropic demixing of polymer rings in the presence of mobile crowders and determine the characteristic times of the internal polymer dynamics. Effects of the ring length on ring-ring overlap are also analyzed. In particular, on systematic variation of the fraction of crowding molecules, a (1 - phi)-scaling is found for the ring-ring overlap length along the cylinder axis, and a non-monotonic dependence of the 3D ring-ring contact number with a maximum at phi approximate to 0.2 is obtained. Our results demonstrate that polymer rings are demixed and separated by particular entropy-favourable partitioning of crowders along the axis of the cylindrical simulation box. These findings help to rationalize the implications of macromolecular crowding for circular DNA molecules in confined spaces inside bacteria as well as in localized cellular compartments inside eukaryotic cells. KW - polymers KW - confinement KW - crowding Y1 - 2014 U6 - https://doi.org/10.1088/1367-2630/16/5/053047 SN - 1367-2630 VL - 16 PB - IOP Publ. Ltd. CY - Bristol ER - TY - JOUR A1 - Godec, Aljaz A1 - Chechkin, Aleksei V. A1 - Barkai, Eli A1 - Kantz, Holger A1 - Metzler, Ralf T1 - Localisation and universal fluctuations in ultraslow diffusion processes JF - Journal of physics : A, Mathematical and theoretical N2 - We study ultraslow diffusion processes with logarithmic mean squared displacement (MSD) < x(2)(t)> similar or equal to log(gamma)t. Comparison of annealed (renewal) continuous time random walks (CTRWs) with logarithmic waiting time distribution psi(tau) similar or equal to 1/(tau log(1+gamma)tau) and Sinai diffusion in quenched random landscapes reveals striking similarities, despite the great differences in their physical nature. In particular, they exhibit a weakly non-ergodic disparity of the time-averaged and ensemble-averaged MSDs. Remarkably, for the CTRW we observe that the fluctuations of time averages become universal, with an exponential suppression of mobile trajectories. We discuss the fundamental connection between the Golosov localization effect and non-ergodicity in the sense of the disparity between ensemble-averaged MSD and time-averaged MSD. KW - Sinai diffusion KW - anomalous diffusion KW - quenched energy landscape Y1 - 2014 U6 - https://doi.org/10.1088/1751-8113/47/49/492002 SN - 1751-8113 SN - 1751-8121 VL - 47 IS - 49 PB - IOP Publ. Ltd. CY - Bristol ER - TY - JOUR A1 - Cherstvy, Andrey G. A1 - Chechkin, Aleksei V. A1 - Metzler, Ralf T1 - Ageing and confinement in non-ergodic heterogeneous diffusion processes JF - Journal of physics : A, Mathematical and theoretical N2 - We study the effects of ageing-the time delay between initiation of the physical process at t = 0 and start of observation at some time t(a) > 0-and spatial confinement on the properties of heterogeneous diffusion processes (HDPs) with deterministic power-law space-dependent diffusivities, D(x) = D-0 vertical bar x vertical bar(alpha). From analysis of the ensemble and time averaged mean squared displacements and the ergodicity breaking parameter quantifying the inherent degree of irreproducibility of individual realizations of the HDP we obtain striking similarities to ageing subdiffusive continuous time random walks with scale-free waiting time distributions. We also explore how both processes can be distinguished. For confined HDPs we study the long-time saturation of the ensemble and time averaged particle displacements as well as the magnitude of the inherent scatter of time averaged displacements and contrast the outcomes to the results known for other anomalous diffusion processes under confinement. KW - stochastic processes KW - anomalous diffusion KW - ageing KW - weak ergodicity breaking Y1 - 2014 U6 - https://doi.org/10.1088/1751-8113/47/48/485002 SN - 1751-8113 SN - 1751-8121 VL - 47 IS - 48 PB - IOP Publ. Ltd. CY - Bristol ER - TY - JOUR A1 - Shin, Jaeoh A1 - Cherstvy, Andrey G. A1 - Metzler, Ralf T1 - Sensing viruses by mechanical tension of DNA in responsive hydrogels JF - Physical review : X, Expanding access N2 - The rapid worldwide spread of severe viral infections, often involving novel mutations of viruses, poses major challenges to our health-care systems. This means that tools that can efficiently and specifically diagnose viruses are much needed. To be relevant for broad applications in local health-care centers, such tools should be relatively cheap and easy to use. In this paper, we discuss the biophysical potential for the macroscopic detection of viruses based on the induction of a mechanical stress in a bundle of prestretched DNA molecules upon binding of viruses to the DNA. We show that the affinity of the DNA to the charged virus surface induces a local melting of the double helix into two single-stranded DNA. This process effects a mechanical stress along the DNA chains leading to an overall contraction of the DNA. Our results suggest that when such DNA bundles are incorporated in a supporting matrix such as a responsive hydrogel, the presence of viruses may indeed lead to a significant, macroscopic mechanical deformation of the matrix. We discuss the biophysical basis for this effect and characterize the physical properties of the associated DNA melting transition. In particular, we reveal several scaling relations between the relevant physical parameters of the system. We promote this DNA-based assay as a possible tool for efficient and specific virus screening. Y1 - 2014 U6 - https://doi.org/10.1103/PhysRevX.4.021002 SN - 2160-3308 VL - 4 IS - 2 PB - American Physical Society CY - College Park ER - TY - JOUR A1 - Krüsemann, Henning A1 - Godec, Aljaz A1 - Metzler, Ralf T1 - First-passage statistics for aging diffusion in systems with annealed and quenched disorder JF - Physical review : E, Statistical, nonlinear and soft matter physics N2 - Aging, the dependence of the dynamics of a physical process on the time t(a) since its original preparation, is observed in systems ranging from the motion of charge carriers in amorphous semiconductors over the blinking dynamics of quantum dots to the tracer dispersion in living biological cells. Here we study the effects of aging on one of the most fundamental properties of a stochastic process, the first-passage dynamics. We find that for an aging continuous time random walk process, the scaling exponent of the density of first-passage times changes twice as the aging progresses and reveals an intermediate scaling regime. The first-passage dynamics depends on t(a) differently for intermediate and strong aging. Similar crossovers are obtained for the first-passage dynamics for a confined and driven particle. Comparison to the motion of an aged particle in the quenched trap model with a bias shows excellent agreement with our analytical findings. Our results demonstrate how first-passage measurements can be used to unravel the age t(a) of a physical system. Y1 - 2014 U6 - https://doi.org/10.1103/PhysRevE.89.040101 SN - 1539-3755 SN - 1550-2376 VL - 89 IS - 4 PB - American Physical Society CY - College Park ER - TY - JOUR A1 - Ghosh, Surya K. A1 - Cherstvy, Andrey G. A1 - Metzler, Ralf T1 - Deformation propagation in responsive polymer network films JF - The journal of chemical physics : bridges a gap between journals of physics and journals of chemistr N2 - We study the elastic deformations in a cross-linked polymer network film triggered by the binding of submicron particles with a sticky surface, mimicking the interactions of viral pathogens with thin films of stimulus-responsive polymeric materials such as hydrogels. From extensive Langevin Dynamics simulations we quantify how far the network deformations propagate depending on the elasticity parameters of the network and the adhesion strength of the particles. We examine the dynamics of the collective area shrinkage of the network and obtain some simple relations for the associated characteristic decay lengths. A detailed analysis elucidates how the elastic energy of the network is distributed between stretching and compression modes in response to the particle binding. We also examine the force-distance curves of the repulsion or attraction interactions for a pair of sticky particles in the polymer network film as a function of the particle-particle separation. The results of this computational study provide new insight into collective phenomena in soft polymer network films and may, in particular, be applied to applications for visual detection of pathogens such as viruses via a macroscopic response of thin films of cross-linked hydrogels. (C) 2014 AIP Publishing LLC. Y1 - 2014 U6 - https://doi.org/10.1063/1.4893056 SN - 0021-9606 SN - 1089-7690 VL - 141 IS - 7 PB - American Institute of Physics CY - Melville ER - TY - JOUR A1 - Goychuk, Igor A1 - Kharchenko, Vasyl O. A1 - Metzler, Ralf T1 - Molecular motors pulling cargos in the viscoelastic cytosol: how power strokes beat subdiffusion JF - Physical chemistry, chemical physics : a journal of European Chemical Societies N2 - The discovery of anomalous diffusion of larger biopolymers and submicron tracers such as endogenous granules, organelles, or virus capsids in living cells, attributed to the viscoelastic nature of the cytoplasm, provokes the question whether this complex environment equally impacts the active intracellular transport of submicron cargos by molecular motors such as kinesins: does the passive anomalous diffusion of free cargo always imply its anomalously slow active transport by motors, the mean transport distance along microtubule growing sublinearly rather than linearly in time? Here we analyze this question within the widely used two-state Brownian ratchet model of kinesin motors based on the continuous-state diffusion along microtubules driven by a flashing binding potential, where the cargo particle is elastically attached to the motor. Depending on the cargo size, the loading force, the amplitude of the binding potential, the turnover frequency of the molecular motor enzyme, and the linker stiffness we demonstrate that the motor transport may turn out either normal or anomalous, as indeed measured experimentally. We show how a highly efficient normal active transport mediated by motors may emerge despite the passive anomalous diffusion of the cargo, and study the intricate effects of the elastic linker. Under different, well specified conditions the microtubule-based motor transport becomes anomalously slow and thus significantly less efficient. Y1 - 2014 U6 - https://doi.org/10.1039/c4cp01234h SN - 1463-9076 SN - 1463-9084 VL - 16 IS - 31 SP - 16524 EP - 16535 PB - Royal Society of Chemistry CY - Cambridge ER - TY - JOUR A1 - Cherstvy, Andrey G. A1 - Chechkin, Aleksei V. A1 - Metzler, Ralf T1 - Particle invasion, survival, and non-ergodicity in 2D diffusion processes with space-dependent diffusivity JF - Soft matter N2 - We study the thermal Markovian diffusion of tracer particles in a 2D medium with spatially varying diffusivity D(r), mimicking recently measured, heterogeneous maps of the apparent diffusion coefficient in biological cells. For this heterogeneous diffusion process (HDP) we analyse the mean squared displacement (MSD) of the tracer particles, the time averaged MSD, the spatial probability density function, and the first passage time dynamics from the cell boundary to the nucleus. Moreover we examine the non-ergodic properties of this process which are important for the correct physical interpretation of time averages of observables obtained from single particle tracking experiments. From extensive computer simulations of the 2D stochastic Langevin equation we present an in-depth study of this HDP. In particular, we find that the MSDs along the radial and azimuthal directions in a circular domain obey anomalous and Brownian scaling, respectively. We demonstrate that the time averaged MSD stays linear as a function of the lag time and the system thus reveals a weak ergodicity breaking. Our results will enable one to rationalise the diffusive motion of larger tracer particles such as viruses or submicron beads in biological cells. Y1 - 2014 U6 - https://doi.org/10.1039/c3sm52846d SN - 1744-683X SN - 1744-6848 VL - 10 IS - 10 SP - 1591 EP - 1601 PB - Royal Society of Chemistry CY - Cambridge ER - TY - JOUR A1 - Goychuk, Igor A. A1 - Kharchenko, Vasyl O. A1 - Metzler, Ralf T1 - Molecular motors pulling cargos in the viscoelastic cytosol: how power strokes beat subdiffusion JF - Physical Chemistry Chemical Physics N2 - The discovery of anomalous diffusion of larger biopolymers and submicron tracers such as endogenous granules, organelles, or virus capsids in living cells, attributed to the viscoelastic nature of the cytoplasm, provokes the question whether this complex environment equally impacts the active intracellular transport of submicron cargos by molecular motors such as kinesins: does the passive anomalous diffusion of free cargo always imply its anomalously slow active transport by motors, the mean transport distance along microtubule growing sublinearly rather than linearly in time? Here we analyze this question within the widely used two-state Brownian ratchet model of kinesin motors based on the continuous-state diffusion along microtubules driven by a flashing binding potential, where the cargo particle is elastically attached to the motor. Depending on the cargo size, the loading force, the amplitude of the binding potential, the turnover frequency of the molecular motor enzyme, and the linker stiffness we demonstrate that the motor transport may turn out either normal or anomalous, as indeed measured experimentally. We show how a highly efficient normal active transport mediated by motors may emerge despite the passive anomalous diffusion of the cargo, and study the intricate effects of the elastic linker. Under different, well specified conditions the microtubule-based motor transport becomes anomalously slow and thus significantly less efficient. KW - royal soc chemistry KW - thomas graham house KW - science park KW - milton rd KW - cambridge cb4 0wf KW - cambs KW - england Y1 - 2014 SN - 1463-9076 IS - 16 SP - 16524 EP - 16535 PB - the Royal Society of Chemistry CY - Cambridge ER - TY - JOUR A1 - Bauer, Maximilian A1 - Godec, Aljaž A1 - Metzler, Ralf T1 - Diffusion of finite-size particles in two-dimensional channels with random wall configurations JF - Physical chemistry, chemical physics : PCCP ; a journal of European chemical societies N2 - Diffusion of chemicals or tracer molecules through complex systems containing irregularly shaped channels is important in many applications. Most theoretical studies based on the famed Fick–Jacobs equation focus on the idealised case of infinitely small particles and reflecting boundaries. In this study we use numerical simulations to consider the transport of finite-size particles through asymmetrical two-dimensional channels. Additionally, we examine transient binding of the molecules to the channel walls by applying sticky boundary conditions. We consider an ensemble of particles diffusing in independent channels, which are characterised by common structural parameters. We compare our results for the long-time effective diffusion coefficient with a recent theoretical formula obtained by Dagdug and Pineda [J. Chem. Phys., 2012, 137, 024107]. KW - anomalous diffusion KW - fractional dynamics KW - transport KW - nonergodicity KW - coefficient Y1 - 2014 U6 - https://doi.org/10.1039/C3CP55160A SN - 1463-9084 SN - 1463-9076 VL - 16 IS - 13 SP - 6118 EP - 6128 PB - RSC Publications CY - Cambridge ER - TY - JOUR A1 - Sandev, Trifce A1 - Metzler, Ralf A1 - Tomovski, Zivorad T1 - Correlation functions for the fractional generalized Langevin equation in the presence of internal and external noise JF - Journal of mathematical physics N2 - We study generalized fractional Langevin equations in the presence of a harmonic potential. General expressions for the mean velocity and particle displacement, the mean squared displacement, position and velocity correlation functions, as well as normalized displacement correlation function are derived. We report exact results for the cases of internal and external friction, that is, when the driving noise is either internal and thus the fluctuation-dissipation relation is fulfilled or when the noise is external. The asymptotic behavior of the generalized stochastic oscillator is investigated, and the case of high viscous damping (overdamped limit) is considered. Additional behaviors of the normalized displacement correlation functions different from those for the regular damped harmonic oscillator are observed. In addition, the cases of a constant external force and the force free case are obtained. The validity of the generalized Einstein relation for this process is discussed. The considered fractional generalized Langevin equation may be used to model anomalous diffusive processes including single file-type diffusion. Y1 - 2014 U6 - https://doi.org/10.1063/1.4863478 SN - 0022-2488 SN - 1089-7658 VL - 55 IS - 2 PB - American Institute of Physics CY - Melville ER - TY - JOUR A1 - Eliazar, Iddo A1 - Metzler, Ralf T1 - Anomalous statistics of random relaxations in random environments JF - Physical review : E, Statistical, nonlinear and soft matter physics N2 - We comprehensively analyze the emergence of anomalous statistics in the context of the random relaxation ( RARE) model [Eliazar and Metzler, J. Chem. Phys. 137, 234106 ( 2012)], a recently introduced versatile model of random relaxations in random environments. The RARE model considers excitations scattered randomly across a metric space around a reaction center. The excitations react randomly with the center, the reaction rates depending on the excitations' distances from this center. Relaxation occurs upon the first reaction between an excitation and the center. Addressing both the relaxation time and the relaxation range, we explore when these random variables display anomalous statistics, namely, heavy tails at zero and at infinity that manifest, respectively, exceptionally high occurrence probabilities of very small and very large outliers. A cohesive set of closed-form analytic results is established, determining precisely when such anomalous statistics emerge. Y1 - 2013 U6 - https://doi.org/10.1103/PhysRevE.87.022141 SN - 1539-3755 SN - 1550-2376 VL - 87 IS - 2 PB - American Physical Society CY - College Park ER - TY - JOUR A1 - Kursawe, Jochen A1 - Schulz, Johannes H. P. A1 - Metzler, Ralf T1 - Transient aging in fractional brownian and langevin-equation motion JF - Physical review : E, Statistical, nonlinear and soft matter physics N2 - Stochastic processes driven by stationary fractional Gaussian noise, that is, fractional Brownian motion and fractional Langevin-equation motion, are usually considered to be ergodic in the sense that, after an algebraic relaxation, time and ensemble averages of physical observables coincide. Recently it was demonstrated that fractional Brownian motion and fractional Langevin-equation motion under external confinement are transiently nonergodic-time and ensemble averages behave differently-from the moment when the particle starts to sense the confinement. Here we show that these processes also exhibit transient aging, that is, physical observables such as the time-averaged mean-squared displacement depend on the time lag between the initiation of the system at time t = 0 and the start of the measurement at the aging time t(a). In particular, it turns out that for fractional Langevin-equation motion the aging dependence on ta is different between the cases of free and confined motion. We obtain explicit analytical expressions for the aged moments of the particle position as well as the time-averaged mean-squared displacement and present a numerical analysis of this transient aging phenomenon. Y1 - 2013 U6 - https://doi.org/10.1103/PhysRevE.88.062124 SN - 1539-3755 SN - 1550-2376 VL - 88 IS - 6 PB - American Physical Society CY - College Park ER - TY - JOUR A1 - Bauer, Maximilian A1 - Metzler, Ralf T1 - In vivo facilitated diffusion model JF - PLoS one N2 - Under dilute in vitro conditions transcription factors rapidly locate their target sequence on DNA by using the facilitated diffusion mechanism. However, whether this strategy of alternating between three-dimensional bulk diffusion and one-dimensional sliding along the DNA contour is still beneficial in the crowded interior of cells is highly disputed. Here we use a simple model for the bacterial genome inside the cell and present a semi-analytical model for the in vivo target search of transcription factors within the facilitated diffusion framework. Without having to resort to extensive simulations we determine the mean search time of a lac repressor in a living E. coli cell by including parameters deduced from experimental measurements. The results agree very well with experimental findings, and thus the facilitated diffusion picture emerges as a quantitative approach to gene regulation in living bacteria cells. Furthermore we see that the search time is not very sensitive to the parameters characterizing the DNA configuration and that the cell seems to operate very close to optimal conditions for target localization. Local searches as implied by the colocalization mechanism are only found to mildly accelerate the mean search time within our model. Y1 - 2013 U6 - https://doi.org/10.1371/journal.pone.0053956 SN - 1932-6203 VL - 8 IS - 1 PB - PLoS CY - San Fransisco ER - TY - JOUR A1 - Godec, Aljaz A1 - Metzler, Ralf T1 - Finite-Time effects and ultraweak ergodicity breaking in superdiffusive dynamics JF - Physical review letters N2 - We study the ergodic properties of superdiffusive, spatiotemporally coupled Levy walk processes. For trajectories of finite duration, we reveal a distinct scatter of the scaling exponents of the time averaged mean squared displacement (delta x(2)) over bar around the ensemble value 3 - alpha (1 < alpha < 2) ranging from ballistic motion to subdiffusion, in strong contrast to the behavior of subdiffusive processes. In addition we find a significant dependence of the average of (delta x(2)) over bar over an ensemble of trajectories as a function of the finite measurement time. This so-called finite-time amplitude depression and the scatter of the scaling exponent is vital in the quantitative evaluation of superdiffusive processes. Comparing the long time average of the second moment with the ensemble mean squared displacement, these only differ by a constant factor, an ultraweak ergodicity breaking. Y1 - 2013 U6 - https://doi.org/10.1103/PhysRevLett.110.020603 SN - 0031-9007 VL - 110 IS - 2 PB - American Physical Society CY - College Park ER - TY - JOUR A1 - Schulz, Johannes H. P. A1 - Barkai, Eli A1 - Metzler, Ralf T1 - Aging effects and population splitting in single-particle trajectoryaverages JF - Physical review letters N2 - We study time averages of single particle trajectories in scale-free anomalous diffusion processes, in which the measurement starts at some time t(a) > 0 after initiation of the process at t = 0. Using aging renewal theory, we show that for such nonstationary processes a large class of observables are affected by a unique aging function, which is independent of boundary conditions or the external forces. Moreover, we discuss the implications of aging induced population splitting: with growing age ta of the process, an increasing fraction of particles remains motionless in a measurement of fixed duration. Consequences for single biomolecule tracking in live cells are discussed. Y1 - 2013 U6 - https://doi.org/10.1103/PhysRevLett.110.020602 SN - 0031-9007 SN - 1079-7114 VL - 110 IS - 2 PB - American Physical Society CY - College Park ER - TY - JOUR A1 - Cherstvy, Andrey G. A1 - Metzler, Ralf T1 - Population splitting, trapping, and non-ergodicity in heterogeneous diffusion processes JF - Physical chemistry, chemical physics : a journal of European Chemical Societies N2 - We consider diffusion processes with a spatially varying diffusivity giving rise to anomalous diffusion. Such heterogeneous diffusion processes are analysed for the cases of exponential, power-law, and logarithmic dependencies of the diffusion coefficient on the particle position. Combining analytical approaches with stochastic simulations, we show that the functional form of the space-dependent diffusion coefficient and the initial conditions of the diffusing particles are vital for their statistical and ergodic properties. In all three cases a weak ergodicity breaking between the time and ensemble averaged mean squared displacements is observed. We also demonstrate a population splitting of the time averaged traces into fast and slow diffusers for the case of exponential variation of the diffusivity as well as a particle trapping in the case of the logarithmic diffusivity. Our analysis is complemented by the quantitative study of the space coverage, the diffusive spreading of the probability density, as well as the survival probability. Y1 - 2013 U6 - https://doi.org/10.1039/c3cp53056f SN - 1463-9076 SN - 1463-9084 VL - 15 IS - 46 SP - 20220 EP - 20235 PB - Royal Society of Chemistry CY - Cambridge ER - TY - JOUR A1 - Vahabi, Mahsa A1 - Schulz, Johannes H. P. A1 - Shokri, Babak A1 - Metzler, Ralf T1 - Area coverage of radial Levy flights with periodic boundary conditions JF - Physical review : E, Statistical, nonlinear and soft matter physics N2 - We consider the area coverage of radial Levy flights in a finite square area with periodic boundary conditions. From simulations we show how the fractal path dimension d(f) and thus the degree of area coverage depends on the number of steps of the trajectory, the size of the area, and the resolution of the applied box counting algorithm. For sufficiently long trajectories and not too high resolution, the fractal dimension returned by the box counting method equals two, and in that sense the Levy flight fully covers the area. Otherwise, the determined fractal dimension equals the stable index of the distribution of jump lengths of the Levy flight. We provide mathematical expressions for the turnover between these two scaling regimes. As complementary methods to analyze confined Levy flights we investigate fractional order moments of the position for which we also provide scaling arguments. Finally, we study the time evolution of the probability density function and the first passage time density of Levy flights in a square area. Our findings are of interest for a general understanding of Levy flights as well as for the analysis of recorded trajectories of animals searching for food or for human motion patterns. Y1 - 2013 U6 - https://doi.org/10.1103/PhysRevE.87.042136 SN - 1539-3755 VL - 87 IS - 4 PB - American Physical Society CY - College Park ER - TY - JOUR A1 - Jeon, Jae-Hyung A1 - Leijnse, Natascha A1 - Oddershede, Lene B. A1 - Metzler, Ralf T1 - Anomalous diffusion and power-law relaxation of the time averaged mean squared displacement in worm-like micellar solutions JF - New journal of physics : the open-access journal for physics N2 - We report the results of single tracer particle tracking by optical tweezers and video microscopy in micellar solutions. From careful analysis in terms of different stochastic models, we show that the polystyrene tracer beads of size 0.52-2.5 mu m after short-time normal diffusion turn over to perform anomalous diffusion of the form < r(2)(t)> similar or equal to t(alpha) with alpha approximate to 0.3. This free anomalous diffusion is ergodic and consistent with a description in terms of the generalized Langevin equation with a power-law memory kernel. With optical tweezers tracking, we unveil a power-law relaxation over several decades in time to the thermal plateau value under the confinement of the harmonic tweezer potential, as predicted previously (Phys. Rev. E 85 021147 (2012)). After the subdiffusive motion in the millisecond range, the motion becomes faster and turns either back to normal Brownian diffusion or to even faster superdiffusion, depending on the size of the tracer beads. Y1 - 2013 U6 - https://doi.org/10.1088/1367-2630/15/4/045011 SN - 1367-2630 VL - 15 IS - 4 PB - IOP Publ. Ltd. CY - Bristol ER - TY - JOUR A1 - Maity, Alok Kumar A1 - Bandyopadhyay, Arnab A1 - Chattopadhyay, Sudip A1 - Chaudhuri, Jyotipratim Ray A1 - Metzler, Ralf A1 - Chaudhury, Pinaki A1 - Banik, Suman K. T1 - Quantification of noise in bifunctionality-induced post-translational modification JF - Physical review : E, Statistical, nonlinear and soft matter physics N2 - We present a generic analytical scheme for the quantification of fluctuations due to bifunctionality-induced signal transduction within the members of a bacterial two-component system. The proposed model takes into account post-translational modifications in terms of elementary phosphotransfer kinetics. Sources of fluctuations due to autophosphorylation, kinase, and phosphatase activity of the sensor kinase have been considered in the model via Langevin equations, which are then solved within the framework of linear noise approximation. The resultant analytical expression of phosphorylated response regulators are then used to quantify the noise profile of biologically motivated single and branched pathways. Enhancement and reduction of noise in terms of extra phosphate outflux and influx, respectively, have been analyzed for the branched system. Furthermore, the role of fluctuations of the network output in the regulation of a promoter with random activation-deactivation dynamics has been analyzed. Y1 - 2013 U6 - https://doi.org/10.1103/PhysRevE.88.032716 SN - 1539-3755 VL - 88 IS - 3 PB - American Physical Society CY - College Park ER - TY - JOUR A1 - Jeon, Jae-Hyung A1 - Barkai, Eli A1 - Metzler, Ralf T1 - Noisy continuous time random walks JF - The journal of chemical physics : bridges a gap between journals of physics and journals of chemistr N2 - Experimental studies of the diffusion of biomolecules within biological cells are routinely confronted with multiple sources of stochasticity, whose identification renders the detailed data analysis of single molecule trajectories quite intricate. Here, we consider subdiffusive continuous time random walks that represent a seminal model for the anomalous diffusion of tracer particles in complex environments. This motion is characterized by multiple trapping events with infinite mean sojourn time. In real physical situations, however, instead of the full immobilization predicted by the continuous time random walk model, the motion of the tracer particle shows additional jiggling, for instance, due to thermal agitation of the environment. We here present and analyze in detail an extension of the continuous time random walk model. Superimposing the multiple trapping behavior with additive Gaussian noise of variable strength, we demonstrate that the resulting process exhibits a rich variety of apparent dynamic regimes. In particular, such noisy continuous time random walks may appear ergodic, while the bare continuous time random walk exhibits weak ergodicity breaking. Detailed knowledge of this behavior will be useful for the truthful physical analysis of experimentally observed subdiffusion. Y1 - 2013 U6 - https://doi.org/10.1063/1.4816635 SN - 0021-9606 SN - 1089-7690 VL - 139 IS - 12 PB - American Institute of Physics CY - Melville ER - TY - JOUR A1 - Schulz, Johannes H. P. A1 - Chechkin, Aleksei V. A1 - Metzler, Ralf T1 - Correlated continuous time random walks - combining scale-invariance with long-range memory for spatial and temporal dynamics JF - Journal of physics : A, Mathematical and theoretical N2 - Standard continuous time random walk (CTRW) models are renewal processes in the sense that at each jump a new, independent pair of jump length and waiting time are chosen. Globally, anomalous diffusion emerges through scale-free forms of the jump length and/or waiting time distributions by virtue of the generalized central limit theorem. Here we present a modified version of recently proposed correlated CTRW processes, where we incorporate a power-law correlated noise on the level of both jump length and waiting time dynamics. We obtain a very general stochastic model, that encompasses key features of several paradigmatic models of anomalous diffusion: discontinuous, scale-free displacements as in Levy flights, scale-free waiting times as in subdiffusive CTRWs, and the long-range temporal correlations of fractional Brownian motion (FBM). We derive the exact solutions for the single-time probability density functions and extract the scaling behaviours. Interestingly, we find that different combinations of the model parameters lead to indistinguishable shapes of the emerging probability density functions and identical scaling laws. Our model will be useful for describing recent experimental single particle tracking data that feature a combination of CTRW and FBM properties. Y1 - 2013 U6 - https://doi.org/10.1088/1751-8113/46/47/475001 SN - 1751-8113 SN - 1751-8121 VL - 46 IS - 47 PB - IOP Publ. Ltd. CY - Bristol ER - TY - JOUR A1 - Cherstvy, Andrey G. A1 - Chechkin, Aleksei V. A1 - Metzler, Ralf T1 - Anomalous diffusion and ergodicity breaking in heterogeneous diffusion processes JF - New journal of physics : the open-access journal for physics N2 - We demonstrate the non-ergodicity of a simple Markovian stochastic process with space-dependent diffusion coefficient D(x). For power-law forms D(x) similar or equal to vertical bar x vertical bar(alpha), this process yields anomalous diffusion of the form < x(2)(t)> similar or equal to t(2/(2-alpha)). Interestingly, in both the sub- and superdiffusive regimes we observe weak ergodicity breaking: the scaling of the time-averaged mean-squared displacement <(delta(2)(Delta))over bar> remains linear in the lag time Delta and thus differs from the corresponding ensemble average < x(2)(t)>. We analyse the non-ergodic behaviour of this process in terms of the time-averaged mean- squared displacement (delta(2)) over bar and its random features, i.e. the statistical distribution of (delta(2)) over bar and the ergodicity breaking parameters. The heterogeneous diffusion model represents an alternative approach to non- ergodic, anomalous diffusion that might be particularly relevant for diffusion in heterogeneous media. Y1 - 2013 U6 - https://doi.org/10.1088/1367-2630/15/8/083039 SN - 1367-2630 VL - 15 IS - 15 PB - IOP Publ. Ltd. CY - Bristol ER - TY - JOUR A1 - Lomholt, Michael A. A1 - Lizana, Ludvig A1 - Metzler, Ralf A1 - Ambjoernsson, Tobias T1 - Microscopic origin of the logarithmic time evolution of aging processes in complex systems JF - Physical review letters N2 - There exists compelling experimental evidence in numerous systems for logarithmically slow time evolution, yet its full theoretical understanding remains elusive. We here introduce and study a generic transition process in complex systems, based on nonrenewal, aging waiting times. Each state n of the system follows a local clock initiated at t = 0. The random time tau between clock ticks follows the waiting time density psi (tau). Transitions between states occur only at local clock ticks and are hence triggered by the local forward waiting time, rather than by psi (tau). For power-law forms psi (tau) similar or equal to tau(-1-alpha) (0 < alpha < 1) we obtain a logarithmic time evolution of the state number < n(t)> similar or equal to log(t/t(0)), while for alpha > 2 the process becomes normal in the sense that < n(t)> similar or equal to t. In the intermediate range 1 < alpha < 2 we find the power-law growth < n(t)> similar or equal to t(alpha-1). Our model provides a universal description for transition dynamics between aging and nonaging states. Y1 - 2013 U6 - https://doi.org/10.1103/PhysRevLett.110.208301 SN - 0031-9007 VL - 110 IS - 20 PB - American Physical Society CY - College Park ER - TY - JOUR A1 - Pulkkinen, Otto A1 - Metzler, Ralf T1 - Distance matters the impact of gene proximity in bacterial gene regulation JF - Physical review letters N2 - Following recent discoveries of colocalization of downstream-regulating genes in living cells, the impact of the spatial distance between such genes on the kinetics of gene product formation is increasingly recognized. We here show from analytical and numerical analysis that the distance between a transcription factor (TF) gene and its target gene drastically affects the speed and reliability of transcriptional regulation in bacterial cells. For an explicit model system, we develop a general theory for the interactions between a TF and a transcription unit. The observed variations in regulation efficiency are linked to the magnitude of the variation of the TF concentration peaks as a function of the binding site distance from the signal source. Our results support the role of rapid binding site search for gene colocalization and emphasize the role of local concentration differences. Y1 - 2013 U6 - https://doi.org/10.1103/PhysRevLett.110.198101 SN - 0031-9007 VL - 110 IS - 19 PB - American Physical Society CY - College Park ER - TY - JOUR A1 - Javanainen, Matti A1 - Hammaren, Henrik A1 - Monticelli, Luca A1 - Jeon, Jae-Hyung A1 - Miettinen, Markus S. A1 - Martinez-Seara, Hector A1 - Metzler, Ralf A1 - Vattulainen, Ilpo T1 - Anomalous and normal diffusion of proteins and lipids in crowded lipid membranes JF - Faraday discussions N2 - Lateral diffusion plays a crucial role in numerous processes that take place in cell membranes, yet it is quite poorly understood in native membranes characterized by, e.g., domain formation and large concentration of proteins. In this article, we use atomistic and coarse-grained simulations to consider how packing of membranes and crowding with proteins affect the lateral dynamics of lipids and membrane proteins. We find that both packing and protein crowding have a profound effect on lateral diffusion, slowing it down. Anomalous diffusion is observed to be an inherent property in both protein-free and protein-rich membranes, and the time scales of anomalous diffusion and the exponent associated with anomalous diffusion are found to strongly depend on packing and crowding. Crowding with proteins also has a striking effect on the decay rate of dynamical correlations associated with lateral single-particle motion, as the transition from anomalous to normal diffusion is found to take place at macroscopic time scales: while in protein-poor conditions normal diffusion is typically observed in hundreds of nanoseconds, in protein-rich conditions the onset of normal diffusion is tens of microseconds, and in the most crowded systems as large as milliseconds. The computational challenge which results from these time scales is not easy to deal with, not even in coarse-grained simulations. We also briefly discuss the physical limits of protein motion. Our results suggest that protein concentration is anything but constant in the plane of cell membranes. Instead, it is strongly dependent on proteins' preference for aggregation. Y1 - 2013 U6 - https://doi.org/10.1039/c2fd20085f SN - 1359-6640 VL - 161 IS - 1 SP - 397 EP - 417 PB - Royal Society of Chemistry CY - Cambridge ER - TY - JOUR A1 - Mattos, Thiago G. A1 - Mejia-Monasterio, Carlos A1 - Metzler, Ralf A1 - Oshanin, Gleb T1 - First passages in bounded domains When is the mean first passage time meaningful? JF - Physical review : E, Statistical, nonlinear and soft matter physics N2 - We study the first passage statistics to adsorbing boundaries of a Brownian motion in bounded two-dimensional domains of different shapes and configurations of the adsorbing and reflecting boundaries. From extensive numerical analysis we obtain the probability P(omega) distribution of the random variable omega = tau(1)/(tau(1) + tau(2)), which is a measure for how similar the first passage times tau(1) and tau(2) are of two independent realizations of a Brownian walk starting at the same location. We construct a chart for each domain, determining whether P(omega) represents a unimodal, bell-shaped form, or a bimodal, M-shaped behavior. While in the former case the mean first passage time (MFPT) is a valid characteristic of the first passage behavior, in the latter case it is an insufficient measure for the process. Strikingly we find a distinct turnover between the two modes of P(omega), characteristic for the domain shape and the respective location of absorbing and reflective boundaries. Our results demonstrate that large fluctuations of the first passage times may occur frequently in two-dimensional domains, rendering quite vague the general use of the MFPT as a robust measure of the actual behavior even in bounded domains, in which all moments of the first passage distribution exist. Y1 - 2012 U6 - https://doi.org/10.1103/PhysRevE.86.031143 SN - 1539-3755 VL - 86 IS - 3 PB - American Physical Society CY - College Park ER - TY - JOUR A1 - Jeon, Jae-Hyung A1 - Metzler, Ralf T1 - Inequivalence of time and ensemble averages in ergodic systems: exponential versus power-law relaxation in confinement JF - Physical review : E, Statistical, nonlinear and soft matter physics N2 - Single-particle tracking has become a standard tool for the investigation of diffusive properties, especially in small systems such as biological cells. Usually the resulting time series are analyzed in terms of time averages over individual trajectories. Here we study confined normal as well as anomalous diffusion, modeled by fractional Brownian motion and the fractional Langevin equation, and show that even for such ergodic systems time-averaged quantities behave differently from their ensemble-averaged counterparts, irrespective of how long the measurement time becomes. Knowledge of the exact behavior of time averages is therefore fundamental for the proper physical interpretation of measured time series, in particular, for extraction of the relaxation time scale from data. Y1 - 2012 U6 - https://doi.org/10.1103/PhysRevE.85.021147 SN - 1539-3755 VL - 85 IS - 2 PB - American Physical Society CY - College Park ER - TY - JOUR A1 - Palyulin, Vladimir V. A1 - Metzler, Ralf T1 - How a finite potential barrier decreases the mean first-passage time JF - Journal of statistical mechanics: theory and experiment N2 - We consider the mean first-passage time of a random walker moving in a potential landscape on a finite interval, the starting and end points being at different potentials. From analytical calculations and Monte Carlo simulations we demonstrate that the mean first-passage time for a piecewise linear curve between these two points is minimized by the introduction of a potential barrier. Due to thermal fluctuations, this barrier may be crossed. It turns out that the corresponding expense for this activation is less severe than the gain from an increased slope towards the end point. In particular, the resulting mean first-passage time is shorter than for a linear potential drop between the two points. KW - diffusion Y1 - 2012 U6 - https://doi.org/10.1088/1742-5468/2012/03/L03001 SN - 1742-5468 IS - 1 PB - IOP Publ. Ltd. CY - Bristol ER - TY - JOUR A1 - Magdziarz, Marcin A1 - Metzler, Ralf A1 - Szczotka, Wladyslaw A1 - Zebrowski, Piotr T1 - Correlated continuous-time random walks-scaling limits and Langevin picture JF - Journal of statistical mechanics: theory and experiment N2 - In this paper we analyze correlated continuous-time random walks introduced recently by Tejedor and Metzler (2010 J. Phys. A: Math. Theor. 43 082002). We obtain the Langevin equations associated with this process and the corresponding scaling limits of their solutions. We prove that the limit processes are self-similar and display anomalous dynamics. Moreover, we extend the model to include external forces. Our results are confirmed by Monte Carlo simulations. KW - stochastic processes (theory) KW - diffusion Y1 - 2012 U6 - https://doi.org/10.1088/1742-5468/2012/04/P04010 SN - 1742-5468 PB - IOP Publ. Ltd. CY - Bristol ER - TY - JOUR A1 - Leijnse, N. A1 - Jeon, J. -H. A1 - Loft, S. A1 - Metzler, Ralf A1 - Oddershede, L. B. T1 - Diffusion inside living human cells JF - European physical journal special topics N2 - Naturally occurring lipid granules diffuse in the cytoplasm and can be used as tracers to map out the viscoelastic landscape inside living cells. Using optical trapping and single particle tracking we found that lipid granules exhibit anomalous diffusion inside human umbilical vein endothelial cells. For these cells the exact diffusional pattern of a particular granule depends on the physiological state of the cell and on the localization of the granule within the cytoplasm. Granules located close to the actin rich periphery of the cell move less than those located towards to the center of the cell or within the nucleus. Also, granules in cells which are stressed by intense laser illumination or which have attached to a surface for a long period of time move in a more restricted fashion than those within healthy cells. For granules diffusing in healthy cells, in regions away from the cell periphery, occurrences of weak ergodicity breaking are observed, similar to the recent observations inside living fission yeast cells [1]. Y1 - 2012 U6 - https://doi.org/10.1140/epjst/e2012-01553-y SN - 1951-6355 VL - 204 IS - 1 SP - 75 EP - 84 PB - Springer CY - Heidelberg ER - TY - JOUR A1 - Magdziarz, Marcin A1 - Metzler, Ralf A1 - Szczotka, Wladyslaw A1 - Zebrowski, Piotr T1 - Correlated continuous-time random walks in external force fields JF - Physical review : E, Statistical, nonlinear and soft matter physics N2 - We study the anomalous diffusion of a particle in an external force field whose motion is governed by nonrenewal continuous time random walks with correlated waiting times. In this model the current waiting time T-i is equal to the previous waiting time Ti-1 plus a small increment. Based on the associated coupled Langevin equations the force field is systematically introduced. We show that in a confining potential the relaxation dynamics follows power-law or stretched exponential pattern, depending on the model parameters. The process obeys a generalized Einstein-Stokes-Smoluchowski relation and observes the second Einstein relation. The stationary solution is of Boltzmann-Gibbs form. The case of an harmonic potential is discussed in some detail. We also show that the process exhibits aging and ergodicity breaking. Y1 - 2012 U6 - https://doi.org/10.1103/PhysRevE.85.051103 SN - 1539-3755 SN - 1550-2376 VL - 85 IS - 5 PB - American Physical Society CY - College Park ER - TY - JOUR A1 - Bauer, Maximilian A1 - Metzler, Ralf T1 - Generalized facilitated diffusion model for DNA-binding proteins with search and recognition states JF - Biophysical journal N2 - Transcription factors (TFs) such as the lac repressor find their target sequence on DNA at remarkably high rates. In the established Berg-von Hippel model for this search process, the TF alternates between three-dimensional diffusion in the bulk solution and one-dimensional sliding along the DNA chain. To overcome the so-called speed-stability paradox, in similar models the TF was considered as being present in two conformations (search state and recognition state) between which it switches stochastically. Combining both the facilitated diffusion model and alternating states, we obtain a generalized model. We explicitly treat bulk excursions for rodlike chains arranged in parallel and consider a simplified model for coiled DNA. Compared to previously considered facilitated diffusion models, corresponding to limiting cases of our generalized model, we surprisingly find a reduced target search rate. Moreover, at optimal conditions there is no longer an equipartition between the time spent by the protein on and off the DNA chain. Y1 - 2012 U6 - https://doi.org/10.1016/j.bpj.2012.04.008 SN - 0006-3495 VL - 102 IS - 10 SP - 2321 EP - 2330 PB - Cell Press CY - Cambridge ER - TY - JOUR A1 - Barkai, Eli A1 - Garini, Yuval A1 - Metzler, Ralf T1 - Strange Kinetics of single molecules in living cells JF - Physics today Y1 - 2012 SN - 0031-9228 VL - 65 IS - 8 SP - 29 EP - 35 PB - American Institute of Physics CY - Melville ER - TY - JOUR A1 - Adamcik, Jozef A1 - Jeon, Jae-Hyung A1 - Karczewski, Konrad J. A1 - Metzler, Ralf A1 - Dietler, Giovanni T1 - Quantifying supercoiling-induced denaturation bubbles in DNA JF - Soft matter N2 - In both eukaryotic and prokaryotic DNA sequences of 30-100 base-pairs rich in AT base-pairs have been identified at which the double helix preferentially unwinds. Such DNA unwinding elements are commonly associated with origins for DNA replication and transcription, and with chromosomal matrix attachment regions. Here we present a quantitative study of local DNA unwinding based on extensive single DNA plasmid imaging. We demonstrate that long-lived single-stranded denaturation bubbles exist in negatively supercoiled DNA, at the expense of partial twist release. Remarkably, we observe a linear relation between the degree of supercoiling and the bubble size, in excellent agreement with statistical modelling. Furthermore, we obtain the full distribution of bubble sizes and the opening probabilities at varying salt and temperature conditions. The results presented herein underline the important role of denaturation bubbles in negatively supercoiled DNA for biological processes such as transcription and replication initiation in vivo. Y1 - 2012 U6 - https://doi.org/10.1039/c2sm26089a SN - 1744-683X VL - 8 IS - 33 SP - 8651 EP - 8658 PB - Royal Society of Chemistry CY - Cambridge ER - TY - JOUR A1 - Jeon, Jae-Hyung A1 - Monne, Hector Martinez-Seara A1 - Javanainen, Matti A1 - Metzler, Ralf T1 - Anomalous diffusion of phospholipids and cholesterols in a lipid bilayer and its origins JF - Physical review letters N2 - Combining extensive molecular dynamics simulations of lipid bilayer systems of varying chemical compositions with single-trajectory analyses, we systematically elucidate the stochastic nature of the lipid motion. We observe subdiffusion over more than 4 orders of magnitude in time, clearly stretching into the submicrosecond domain. The lipid motion depends on the lipid chemistry, the lipid phase, and especially the presence of cholesterol. We demonstrate that fractional Langevin equation motion universally describes the lipid motion in all phases, including the gel phase, and in the presence of cholesterol. The results underline the relevance of anomalous diffusion in lipid bilayers and the strong effects of the membrane composition. Y1 - 2012 U6 - https://doi.org/10.1103/PhysRevLett.109.188103 SN - 0031-9007 VL - 109 IS - 18 PB - American Physical Society CY - College Park ER - TY - JOUR A1 - Metzler, Ralf A1 - Jeon, Jae-Hyung T1 - The role of ergodicity in anomalous stochastic processes - analysis of single-particle trajectories JF - Physica scripta : an international journal for experimental and theoretical physics N2 - Single-particle experiments produce time series x(t) of individual particle trajectories, frequently revealing anomalous diffusion behaviour. Typically, individual x(t) are evaluated in terms of time-averaged quantities instead of ensemble averages. Here we discuss the behaviour of the time-averaged mean squared displacement of different stochastic processes giving rise to anomalous diffusion. In particular, we pay attention to the ergodic properties of these processes, i.e. the (non)equivalence of time and ensemble averages. Y1 - 2012 U6 - https://doi.org/10.1088/0031-8949/86/05/058510 SN - 0031-8949 VL - 86 IS - 5 PB - IOP Publ. Ltd. CY - Bristol ER - TY - JOUR A1 - Eliazar, Iddo A1 - Metzler, Ralf T1 - The RARE model a generalized approach to random relaxation processes in disordered systems JF - The journal of chemical physics : bridges a gap between journals of physics and journals of chemistr N2 - This paper introduces and analyses a general statistical model, termed the RAndom RElaxations (RARE) model, of random relaxation processes in disordered systems. The model considers excitations that are randomly scattered around a reaction center in a general embedding space. The model's input quantities are the spatial scattering statistics of the excitations around the reaction center, and the chemical reaction rates between the excitations and the reaction center as a function of their mutual distance. The framework of the RARE model is versatile and a detailed stochastic analysis of the random relaxation processes is established. Analytic results regarding the duration and the range of the random relaxation processes, as well as the model's thermodynamic limit, are obtained in closed form. In particular, the case of power-law inputs, which turn out to yield stretched exponential relaxation patterns and asymptotically Paretian relaxation ranges, is addressed in detail. KW - chemical relaxation KW - Pareto analysis KW - reaction kinetics theory KW - reaction rate constants KW - stochastic processes Y1 - 2012 U6 - https://doi.org/10.1063/1.4770266 SN - 0021-9606 SN - 1089-7690 VL - 137 IS - 23 PB - American Institute of Physics CY - Melville ER - TY - JOUR A1 - Sereshki, L. E. A1 - Lomholt, M. A. A1 - Metzler, Ralf T1 - A solution to the subdiffusion-efficiency paradox inactive states enhance reaction efficiency at subdiffusion conditions in living cells JF - epl : a letters journal exploring the frontiers of physics N2 - Macromolecular crowding in living biological cells effects subdiffusion of larger biomolecules such as proteins and enzymes. Mimicking this subdiffusion in terms of random walks on a critical percolation cluster, we here present a case study of EcoRV restriction enzymes involved in vital cellular defence. We show that due to its so far elusive propensity to an inactive state the enzyme avoids non-specific binding and remains well-distributed in the bulk cytoplasm of the cell. Despite the reduced volume exploration capability of subdiffusion processes, this mechanism guarantees a high efficiency of the enzyme. By variation of the non-specific binding constant and the bond occupation probability on the percolation network, we demonstrate that reduced nonspecific binding are beneficial for efficient subdiffusive enzyme activity even in relatively small bacteria cells. Our results corroborate a more local picture of cellular regulation. Y1 - 2012 U6 - https://doi.org/10.1209/0295-5075/97/20008 SN - 0295-5075 VL - 97 IS - 2 PB - EDP Sciences CY - Mulhouse ER - TY - JOUR A1 - Chechkin, Aleksei V. A1 - Zaid, Irwin M. A1 - Lomholt, Michael A. A1 - Sokolov, Igor M. A1 - Metzler, Ralf T1 - Bulk-mediated diffusion on a planar surface full solution JF - Physical review : E, Statistical, nonlinear and soft matter physics N2 - We consider the effective surface motion of a particle that intermittently unbinds from a planar surface and performs bulk excursions. Based on a random-walk approach, we derive the diffusion equations for surface and bulk diffusion including the surface-bulk coupling. From these exact dynamic equations, we analytically obtain the propagator of the effective surface motion. This approach allows us to deduce a superdiffusive, Cauchy-type behavior on the surface, together with exact cutoffs limiting the Cauchy form. Moreover, we study the long-time dynamics for the surface motion. Y1 - 2012 U6 - https://doi.org/10.1103/PhysRevE.86.041101 SN - 1539-3755 VL - 86 IS - 4 PB - American Physical Society CY - College Park ER - TY - JOUR A1 - Sandev, Trifce A1 - Metzler, Ralf A1 - Tomovski, Zivorad T1 - Velocity and displacement correlation functions for fractional generalized Langevin equations JF - Fractional calculus and applied analysis : an international journal for theory and applications N2 - We study analytically a generalized fractional Langevin equation. General formulas for calculation of variances and the mean square displacement are derived. Cases with a three parameter Mittag-Leffler frictional memory kernel are considered. Exact results in terms of the Mittag-Leffler type functions for the relaxation functions, average velocity and average particle displacement are obtained. The mean square displacement and variances are investigated analytically. Asymptotic behaviors of the particle in the short and long time limit are found. The model considered in this paper may be used for modeling anomalous diffusive processes in complex media including phenomena similar to single file diffusion or possible generalizations thereof. We show the importance of the initial conditions on the anomalous diffusive behavior of the particle. KW - fractional generalized Langevin equation KW - frictional memory kernel KW - variances KW - mean square displacement KW - anomalous diffusion Y1 - 2012 U6 - https://doi.org/10.2478/s13540-012-0031-2 SN - 1311-0454 VL - 15 IS - 3 SP - 426 EP - 450 PB - Versita CY - Warsaw ER - TY - JOUR A1 - Tomovski, Zivorad A1 - Sandev, Trifce A1 - Metzler, Ralf A1 - Dubbeldam, Johan T1 - Generalized space-time fractional diffusion equation with composite fractional time derivative JF - Physica : europhysics journal ; A, Statistical mechanics and its applications N2 - We investigate the solution of space-time fractional diffusion equations with a generalized Riemann-Liouville time fractional derivative and Riesz-Feller space fractional derivative. The Laplace and Fourier transform methods are applied to solve the proposed fractional diffusion equation. The results are represented by using the Mittag-Leffler functions and the Fox H-function. Special cases of the initial and boundary conditions are considered. Numerical scheme and Grunwald-Letnikov approximation are also used to solve the space-time fractional diffusion equation. The fractional moments of the fundamental solution of the considered space-time fractional diffusion equation are obtained. Many known results are special cases of those obtained in this paper. We investigate also the solution of a space-time fractional diffusion equations with a singular term of the form delta(x). t-beta/Gamma(1-beta) (beta > 0). KW - Fractional diffusion equation KW - Composite fractional derivative KW - Riesz-Feller fractional derivative KW - Mittag-Leffler functions KW - Fox H-function KW - Fractional moments KW - Asymptotic expansions KW - Grunwald-Letnikov approximation Y1 - 2012 U6 - https://doi.org/10.1016/j.physa.2011.12.035 SN - 0378-4371 SN - 1873-2119 VL - 391 IS - 8 SP - 2527 EP - 2542 PB - Elsevier CY - Amsterdam ER -