TY - JOUR A1 - Grebenkov, Denis S. A1 - Metzler, Ralf A1 - Oshanin, Gleb T1 - A molecular relay race: sequential first-passage events to the terminal reaction centre in a cascade of diffusion controlled processes JF - New Journal of Physics (NJP) N2 - We consider a sequential cascade of molecular first-reaction events towards a terminal reaction centre in which each reaction step is controlled by diffusive motion of the particles. The model studied here represents a typical reaction setting encountered in diverse molecular biology systems, in which, e.g. a signal transduction proceeds via a series of consecutive 'messengers': the first messenger has to find its respective immobile target site triggering a launch of the second messenger, the second messenger seeks its own target site and provokes a launch of the third messenger and so on, resembling a relay race in human competitions. For such a molecular relay race taking place in infinite one-, two- and three-dimensional systems, we find exact expressions for the probability density function of the time instant of the terminal reaction event, conditioned on preceding successful reaction events on an ordered array of target sites. The obtained expressions pertain to the most general conditions: number of intermediate stages and the corresponding diffusion coefficients, the sizes of the target sites, the distances between them, as well as their reactivities are arbitrary. KW - diffusion KW - reaction cascade KW - first passage time Y1 - 2021 U6 - https://doi.org/10.1088/1367-2630/ac1e42 SN - 1367-2630 VL - 23 PB - IOP - Institute of Physics Publishing CY - Bristol ER - TY - GEN A1 - Grebenkov, Denis S. A1 - Metzler, Ralf A1 - Oshanin, Gleb T1 - A molecular relay race: sequential first-passage events to the terminal reaction centre in a cascade of diffusion controlled processes T2 - Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe N2 - We consider a sequential cascade of molecular first-reaction events towards a terminal reaction centre in which each reaction step is controlled by diffusive motion of the particles. The model studied here represents a typical reaction setting encountered in diverse molecular biology systems, in which, e.g. a signal transduction proceeds via a series of consecutive 'messengers': the first messenger has to find its respective immobile target site triggering a launch of the second messenger, the second messenger seeks its own target site and provokes a launch of the third messenger and so on, resembling a relay race in human competitions. For such a molecular relay race taking place in infinite one-, two- and three-dimensional systems, we find exact expressions for the probability density function of the time instant of the terminal reaction event, conditioned on preceding successful reaction events on an ordered array of target sites. The obtained expressions pertain to the most general conditions: number of intermediate stages and the corresponding diffusion coefficients, the sizes of the target sites, the distances between them, as well as their reactivities are arbitrary. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 1159 KW - diffusion KW - reaction cascade KW - first passage time Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-521942 SN - 1866-8372 ER - TY - JOUR A1 - Herrmann, Carl J. J. A1 - Metzler, Ralf T1 - A self-avoiding walk with neural delays as a model of fixational eye movements JF - Scientific reports N2 - Fixational eye movements show scaling behaviour of the positional mean-squared displacement with a characteristic transition from persistence to antipersistence for increasing time-lag. These statistical patterns were found to be mainly shaped by microsaccades (fast, small-amplitude movements). However, our re-analysis of fixational eye-movement data provides evidence that the slow component (physiological drift) of the eyes exhibits scaling behaviour of the mean-squared displacement that varies across human participants. These results suggest that drift is a correlated movement that interacts with microsaccades. Moreover, on the long time scale, the mean-squared displacement of the drift shows oscillations, which is also present in the displacement auto-correlation function. This finding lends support to the presence of time-delayed feedback in the control of drift movements. Based on an earlier non-linear delayed feedback model of fixational eye movements, we propose and discuss different versions of a new model that combines a self-avoiding walk with time delay. As a result, we identify a model that reproduces oscillatory correlation functions, the transition from persistence to antipersistence, and microsaccades. Y1 - 2017 U6 - https://doi.org/10.1038/s41598-017-13489-8 SN - 2045-2322 VL - 7 SP - 1 EP - 17 PB - Springer Nature CY - London ER - TY - GEN A1 - Herrmann, Carl J. J. A1 - Metzler, Ralf T1 - A self-avoiding walk with neural delays as a model of fixational eye movements N2 - Fixational eye movements show scaling behaviour of the positional mean-squared displacement with a characteristic transition from persistence to antipersistence for increasing time-lag. These statistical patterns were found to be mainly shaped by microsaccades (fast, small-amplitude movements). However, our re-analysis of fixational eye-movement data provides evidence that the slow component (physiological drift) of the eyes exhibits scaling behaviour of the mean-squared displacement that varies across human participants. These results suggest that drift is a correlated movement that interacts with microsaccades. Moreover, on the long time scale, the mean-squared displacement of the drift shows oscillations, which is also present in the displacement auto-correlation function. This finding lends support to the presence of time-delayed feedback in the control of drift movements. Based on an earlier non-linear delayed feedback model of fixational eye movements, we propose and discuss different versions of a new model that combines a self-avoiding walk with time delay. As a result, we identify a model that reproduces oscillatory correlation functions, the transition from persistence to antipersistence, and microsaccades. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 392 Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-403742 ER - TY - JOUR A1 - Herrmann, Carl J. J. A1 - Metzler, Ralf A1 - Engbert, Ralf T1 - A self-avoiding walk with neural delays as a model of fixational eye movements JF - Scientific reports N2 - Fixational eye movements show scaling behaviour of the positional mean-squared displacement with a characteristic transition from persistence to antipersistence for increasing time-lag. These statistical patterns were found to be mainly shaped by microsaccades (fast, small-amplitude movements). However, our re-analysis of fixational eye-movement data provides evidence that the slow component (physiological drift) of the eyes exhibits scaling behaviour of the mean-squared displacement that varies across human participants. These results suggest that drift is a correlated movement that interacts with microsaccades. Moreover, on the long time scale, the mean-squared displacement of the drift shows oscillations, which is also present in the displacement auto-correlation function. This finding lends support to the presence of time-delayed feedback in the control of drift movements. Based on an earlier non-linear delayed feedback model of fixational eye movements, we propose and discuss different versions of a new model that combines a self-avoiding walk with time delay. As a result, we identify a model that reproduces oscillatory correlation functions, the transition from persistence to antipersistence, and microsaccades. Y1 - 2017 U6 - https://doi.org/10.1038/s41598-017-13489-8 SN - 2045-2322 VL - 7 PB - Nature Publ. Group CY - London ER - TY - JOUR A1 - Schwarzl, Maria A1 - Godec, Aljaz A1 - Oshanin, Gleb A1 - Metzler, Ralf T1 - A single predator charging a herd of prey: effects of self volume and predator-prey decision-making JF - Journal of physics : A, Mathematical and theoretical N2 - We study the degree of success of a single predator hunting a herd of prey on a two-dimensional square lattice landscape. We explicitly consider the self volume of the prey restraining their dynamics on the lattice. The movement of both predator and prey is chosen to include an intelligent, decision making step based on their respective sighting ranges, the radius in which they can detect the other species (prey cannot recognise each other besides the self volume interaction): after spotting each other the motion of prey and predator turns from a nearest neighbour random walk into directed escape or chase, respectively. We consider a large range of prey densities and sighting ranges and compute the mean first passage time for a predator to catch a prey as well as characterise the effective dynamics of the hunted prey. We find that the prey's sighting range dominates their life expectancy and the predator profits more from a bad eyesight of the prey than from his own good eye sight. We characterise the dynamics in terms of the mean distance between the predator and the nearest prey. It turns out that effectively the dynamics of this distance coordinate can be captured in terms of a simple Ornstein–Uhlenbeck picture. Reducing the many-body problem to a simple two-body problem by imagining predator and nearest prey to be connected by an effective Hookean bond, all features of the model such as prey density and sighting ranges merge into the effective binding constant. KW - first passage process KW - diffusion KW - predator-prey model Y1 - 2016 U6 - https://doi.org/10.1088/1751-8113/49/22/225601 SN - 1751-8113 SN - 1751-8121 VL - 49 PB - IOP Publ. Ltd. CY - Bristol 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 - Guggenberger, Tobias A1 - Chechkin, Aleksei A1 - Metzler, Ralf T1 - Absence of stationary states and non-Boltzmann distributions of fractional Brownian motion in shallow external potentials JF - New journal of physics : the open-access journal for physics N2 - We study the diffusive motion of a particle in a subharmonic potential of the form U(x) = |x|( c ) (0 < c < 2) driven by long-range correlated, stationary fractional Gaussian noise xi ( alpha )(t) with 0 < alpha <= 2. In the absence of the potential the particle exhibits free fractional Brownian motion with anomalous diffusion exponent alpha. While for an harmonic external potential the dynamics converges to a Gaussian stationary state, from extensive numerical analysis we here demonstrate that stationary states for shallower than harmonic potentials exist only as long as the relation c > 2(1 - 1/alpha) holds. We analyse the motion in terms of the mean squared displacement and (when it exists) the stationary probability density function. Moreover we discuss analogies of non-stationarity of Levy flights in shallow external potentials. KW - diffusion KW - Boltzmann distribution KW - fractional Brownian motion Y1 - 2022 U6 - https://doi.org/10.1088/1367-2630/ac7b3c SN - 1367-2630 VL - 24 IS - 7 PB - Dt. Physikalische Ges. CY - [Bad Honnef] ER - TY - JOUR A1 - Kar, Prathitha A1 - Cherstvy, Andrey G. A1 - Metzler, Ralf T1 - Acceleration of bursty multiprotein target search kinetics on DNA by colocalisation JF - Physical chemistry, chemical physics : a journal of European Chemical Societies N2 - Proteins are capable of locating specific targets on DNA by employing a facilitated diffusion process with intermittent 1D and 3D search steps. Gene colocalisation and coregulation-i.e. the spatial proximity of two communicating genes-is one factor capable of accelerating the target search process along the DNA. We perform Monte Carlo computer simulations and demonstrate the benefits of gene colocalisation for minimising the search time in a model DNA-protein system. We use a simple diffusion model to mimic the search for targets by proteins, produced initially in bursts of multiple proteins and performing the first-passage search on the DNA chain. The behaviour of the mean first-passage times to the target is studied as a function of distance between the initial position of proteins and the DNA target position, as well as versus the concentration of proteins. We also examine the properties of bursty target search kinetics for varying physical-chemical protein-DNA binding affinity. Our findings underline the relevance of colocalisation of production and binding sites for protein search inside biological cells. Y1 - 2017 U6 - https://doi.org/10.1039/c7cp06922g SN - 1463-9076 SN - 1463-9084 VL - 20 IS - 12 SP - 7931 EP - 7946 PB - Royal Society of Chemistry CY - Cambridge ER - TY - JOUR A1 - Godec, Aljaz A1 - Metzler, Ralf T1 - Active transport improves the precision of linear long distance molecular signalling JF - Journal of physics : A, Mathematical and theoretical N2 - Molecular signalling in living cells occurs at low copy numbers and is thereby inherently limited by the noise imposed by thermal diffusion. The precision at which biochemical receptors can count signalling molecules is intimately related to the noise correlation time. In addition to passive thermal diffusion, messenger RNA and vesicle-engulfed signalling molecules can transiently bind to molecular motors and are actively transported across biological cells. Active transport is most beneficial when trafficking occurs over large distances, for instance up to the order of 1 metre in neurons. Here we explain how intermittent active transport allows for faster equilibration upon a change in concentration triggered by biochemical stimuli. Moreover, we show how intermittent active excursions induce qualitative changes in the noise in effectively one-dimensional systems such as dendrites. Thereby they allow for significantly improved signalling precision in the sense of a smaller relative deviation in the concentration read-out by the receptor. On the basis of linear response theory we derive the exact mean field precision limit for counting actively transported molecules. We explain how intermittent active excursions disrupt the recurrence in the molecular motion, thereby facilitating improved signalling accuracy. Our results provide a deeper understanding of how recurrence affects molecular signalling precision in biological cells and novel medical-diagnostic devices. KW - noise in biochemical signalling KW - Brownian motion KW - active transport KW - linear response theory KW - fluctuation-dissipation theorem KW - generalised Langevin equation KW - recurrence Y1 - 2016 U6 - https://doi.org/10.1088/1751-8113/49/36/364001 SN - 1751-8113 SN - 1751-8121 VL - 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 - Chechkin, Aleksei V. A1 - Kantz, Holger A1 - Metzler, Ralf T1 - Ageing effects in ultraslow continuous time random walks JF - The European physical journal : B, Condensed matter and complex systems N2 - In ageing systems physical observables explicitly depend on the time span elapsing between the original initiation of the system and the actual start of the recording of the particle motion. We here study the signatures of ageing in the framework of ultraslow continuous time random walk processes with super-heavy tailed waiting time densities. We derive the density for the forward or recurrent waiting time of the motion as function of the ageing time, generalise the Montroll-Weiss equation for this process, and analyse the ageing behaviour of the ensemble and time averaged mean squared displacements. Y1 - 2017 U6 - https://doi.org/10.1140/epjb/e2017-80270-9 SN - 1434-6028 SN - 1434-6036 VL - 90 PB - Springer CY - New York ER - TY - JOUR A1 - Krüsemann, Henning A1 - Godec, Aljaz A1 - Metzler, Ralf T1 - Ageing first passage time density in continuous time random walks and quenched energy landscapes JF - Journal of physics : A, Mathematical and theoretical N2 - We study the first passage dynamics of an ageing stochastic process in the continuous time random walk (CTRW) framework. In such CTRW processes the test particle performs a random walk, in which successive steps are separated by random waiting times distributed in terms of the waiting time probability density function Psi (t) similar or equal to t(-1-alpha) (0 <= alpha <= 2). An ageing stochastic process is defined by the explicit dependence of its dynamic quantities on the ageing time t(a), the time elapsed between its preparation and the start of the observation. Subdiffusive ageing CTRWs with 0 < alpha < 1 describe systems such as charge carriers in amorphous semiconducters, tracer dispersion in geological and biological systems, or the dynamics of blinking quantum dots. We derive the exact forms of the first passage time density for an ageing subdiffusive CTRW in the semi-infinite, confined, and biased case, finding different scaling regimes for weakly, intermediately, and strongly aged systems: these regimes, with different scaling laws, are also found when the scaling exponent is in the range 1 < alpha < 2, for sufficiently long ta. We compare our results with the ageing motion of a test particle in a quenched energy landscape. We test our theoretical results in the quenched landscape against simulations: only when the bias is strong enough, the correlations from returning to previously visited sites become insignificant and the results approach the ageing CTRW results. With small bias or without bias, the ageing effects disappear and a change in the exponent compared to the case of a completely annealed landscape can be found, reflecting the build-up of correlations in the quenched landscape. KW - first passage KW - random walks KW - anomalous diffusion Y1 - 2015 U6 - https://doi.org/10.1088/1751-8113/48/28/285001 SN - 1751-8113 SN - 1751-8121 VL - 48 IS - 28 PB - IOP Publ. Ltd. CY - Bristol ER - TY - JOUR A1 - Kruesemann, Henning A1 - Schwarzl, Richard A1 - Metzler, Ralf T1 - Ageing Scher-Montroll Transport JF - Transport in Porous Media N2 - We study the properties of ageing Scher-Montroll transport in terms of a biased subdiffusive continuous time random walk in which the waiting times between consecutive jumps of the charge carriers are distributed according to the power law probability with . As we show, the dynamical properties of the Scher-Montroll transport depend on the ageing time span between the initial preparation of the system and the start of the observation. The Scher-Montroll transport theory was originally shown to describe the photocurrent in amorphous solids in the presence of an external electric field, but it has since been used in many other fields of physical sciences, in particular also in the geophysical context for the description of the transport of tracer particles in subsurface aquifers. In the absence of ageing () the photocurrent of the classical Scher-Montroll model or the breakthrough curves in the groundwater context exhibit a crossover between two power law regimes in time with the scaling exponents and . In the presence of ageing a new power law regime and an initial plateau regime of the current emerge. We derive the different power law regimes and crossover times of the ageing Scher-Montroll transport and show excellent agreement with simulations of the process. Experimental data of ageing Scher-Montroll transport in polymeric semiconductors are shown to agree well with the predictions of our theory. KW - Anomalous diffusion KW - Ageing KW - Scher-Montroll transport Y1 - 2016 U6 - https://doi.org/10.1007/s11242-016-0686-y SN - 0169-3913 SN - 1573-1634 VL - 115 SP - 327 EP - 344 PB - Springer CY - New York 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 - 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 - 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 - Safdari, Hadiseh A1 - Chechkin, Aleksei V. A1 - Jafari, Gholamreza R. A1 - Metzler, Ralf T1 - Aging scaled Brownian motion JF - Physical review : E, Statistical, nonlinear and soft matter physics N2 - Scaled Brownian motion (SBM) is widely used to model anomalous diffusion of passive tracers in complex and biological systems. It is a highly nonstationary process governed by the Langevin equation for Brownian motion, however, with a power-law time dependence of the noise strength. Here we study the aging properties of SBM for both unconfined and confined motion. Specifically, we derive the ensemble and time averaged mean squared displacements and analyze their behavior in the regimes of weak, intermediate, and strong aging. A very rich behavior is revealed for confined aging SBM depending on different aging times and whether the process is sub- or superdiffusive. We demonstrate that the information on the aging factorizes with respect to the lag time and exhibits a functional form that is identical to the aging behavior of scale-free continuous time random walk processes. While SBM exhibits a disparity between ensemble and time averaged observables and is thus weakly nonergodic, strong aging is shown to effect a convergence of the ensemble and time averaged mean squared displacement. Finally, we derive the density of first passage times in the semi-infinite domain that features a crossover defined by the aging time. Y1 - 2015 U6 - https://doi.org/10.1103/PhysRevE.91.042107 SN - 1539-3755 SN - 1550-2376 VL - 91 IS - 4 PB - American Physical Society CY - College Park ER - TY - JOUR A1 - Safdari, Hadiseh A1 - Cherstvy, Andrey G. A1 - Chechkin, Aleksei V. A1 - Bodrova, Anna A1 - Metzler, Ralf T1 - Aging underdamped scaled Brownian motion BT - Ensemble- and time-averaged particle displacements, nonergodicity, and the failure of the overdamping approximation JF - Physical review : E, Statistical, nonlinear and soft matter physics N2 - We investigate both analytically and by computer simulations the ensemble- and time-averaged, nonergodic, and aging properties of massive particles diffusing in a medium with a time dependent diffusivity. We call this stochastic diffusion process the (aging) underdamped scaled Brownian motion (UDSBM). We demonstrate how the mean squared displacement (MSD) and the time-averaged MSD of UDSBM are affected by the inertial term in the Langevin equation, both at short, intermediate, and even long diffusion times. In particular, we quantify the ballistic regime for the MSD and the time-averaged MSD as well as the spread of individual time-averaged MSD trajectories. One of the main effects we observe is that, both for the MSD and the time-averaged MSD, for superdiffusive UDSBM the ballistic regime is much shorter than for ordinary Brownian motion. In contrast, for subdiffusive UDSBM, the ballistic region extends to much longer diffusion times. Therefore, particular care needs to be taken under what conditions the overdamped limit indeed provides a correct description, even in the long time limit. We also analyze to what extent ergodicity in the Boltzmann-Khinchin sense in this nonstationary system is broken, both for subdiffusive and superdiffusive UDSBM. Finally, the limiting case of ultraslow UDSBM is considered, with a mixed logarithmic and power-law dependence of the ensemble-and time-averaged MSDs of the particles. In the limit of strong aging, remarkably, the ordinary UDSBM and the ultraslow UDSBM behave similarly in the short time ballistic limit. The approaches developed here open ways for considering other stochastic processes under physically important conditions when a finite particle mass and aging in the system cannot be neglected. Y1 - 2017 U6 - https://doi.org/10.1103/PhysRevE.95.012120 SN - 2470-0045 SN - 2470-0053 VL - 95 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 - 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 - Wang, Wei A1 - Cherstvy, Andrey G. A1 - Liu, Xianbin A1 - Metzler, Ralf T1 - Anomalous diffusion and nonergodicity for heterogeneous diffusion processes with fractional Gaussian noise JF - Physical review : E, Statistical, nonlinear and soft matter physics N2 - Heterogeneous diffusion processes (HDPs) feature a space-dependent diffusivity of the form D(x) = D-0|x|(alpha). Such processes yield anomalous diffusion and weak ergodicity breaking, the asymptotic disparity between ensemble and time averaged observables, such as the mean-squared displacement. Fractional Brownian motion (FBM) with its long-range correlated yet Gaussian increments gives rise to anomalous and ergodic diffusion. Here, we study a combined model of HDPs and FBM to describe the particle dynamics in complex systems with position-dependent diffusivity driven by fractional Gaussian noise. This type of motion is, inter alia, relevant for tracer-particle diffusion in biological cells or heterogeneous complex fluids. We show that the long-time scaling behavior predicted theoretically and by simulations for the ensemble-and time-averaged mean-squared displacements couple the scaling exponents alpha of HDPs and the Hurst exponent H of FBM in a characteristic way. Our analysis of the simulated data in terms of the rescaled variable y similar to |x|(1/(2/(2-alpha)))/t(H) coupling particle position x and time t yields a simple, Gaussian probability density function (PDF), PHDP-FBM(y) = e(-y2)/root pi. Its universal shape agrees well with theoretical predictions for both uni- and bimodal PDF distributions. Y1 - 2020 U6 - https://doi.org/10.1103/PhysRevE.102.012146 SN - 2470-0045 SN - 2470-0053 SN - 1063-651X SN - 1539-3755 SN - 2470-0061 VL - 102 IS - 1 SP - 012146-1 EP - 012146-16 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 - GEN A1 - Metzler, Ralf T1 - Anomalous Diffusion in Membranes and the Cytoplasm of Biological Cells T2 - Biophysical journal Y1 - 2017 U6 - https://doi.org/10.1016/j.bpj.2016.11.2577 SN - 0006-3495 SN - 1542-0086 VL - 112 IS - 3 SP - 476A EP - 476A PB - Cell Press CY - Cambridge ER - TY - JOUR A1 - Cherstvy, Andrey G. A1 - Metzler, Ralf T1 - Anomalous diffusion in time-fluctuating non-stationary diffusivity landscapes JF - Physical chemistry, chemical physics : PCCP ; a journal of European chemical societies N2 - We investigate the ensemble and time averaged mean squared displacements for particle diffusion in a simple model for disordered media by assuming that the local diffusivity is both fluctuating in time and has a deterministic average growth or decay in time. In this study we compare computer simulations of the stochastic Langevin equation for this random diffusion process with analytical results. We explore the regimes of normal Brownian motion as well as anomalous diffusion in the sub- and superdiffusive regimes. We also consider effects of the inertial term on the particle motion. The investigation of the resulting diffusion is performed for unconfined and confined motion. Y1 - 2016 U6 - https://doi.org/10.1039/C6CP03101C SN - 1463-9084 SN - 1463-9076 VL - 18 SP - 23840 EP - 23852 PB - RSC Publ. CY - Cambridge ER - TY - GEN A1 - Cherstvy, Andrey G. A1 - Metzler, Ralf T1 - Anomalous diffusion in time-fluctuating non-stationary diffusivity landscapes N2 - We investigate the ensemble and time averaged mean squared displacements for particle diffusion in a simple model for disordered media by assuming that the local diffusivity is both fluctuating in time and has a deterministic average growth or decay in time. In this study we compare computer simulations of the stochastic Langevin equation for this random diffusion process with analytical results. We explore the regimes of normal Brownian motion as well as anomalous diffusion in the sub- and superdiffusive regimes. We also consider effects of the inertial term on the particle motion. The investigation of the resulting diffusion is performed for unconfined and confined motion. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 257 Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-95901 SP - 23840 EP - 23852 ER - TY - JOUR A1 - Cherstvy, Andrey G. A1 - Metzler, Ralf T1 - Anomalous diffusion in time-fluctuating non-stationary diffusivity landscapes JF - Physical chemistry, chemical physics : a journal of European Chemical Societies N2 - We investigate the ensemble and time averaged mean squared displacements for particle diffusion in a simple model for disordered media by assuming that the local diffusivity is both fluctuating in time and has a deterministic average growth or decay in time. In this study we compare computer simulations of the stochastic Langevin equation for this random diffusion process with analytical results. We explore the regimes of normal Brownian motion as well as anomalous diffusion in the sub- and superdiffusive regimes. We also consider effects of the inertial term on the particle motion. The investigation of the resulting diffusion is performed for unconfined and confined motion. Y1 - 2016 U6 - https://doi.org/10.1039/c6cp03101c SN - 1463-9076 SN - 1463-9084 VL - 18 SP - 23840 EP - 23852 PB - Royal Society of Chemistry CY - Cambridge ER - TY - JOUR A1 - Metzler, Ralf A1 - Jeon, Jae-Hyung A1 - Cherstvy, Andrey G. A1 - Barkai, Eli T1 - Anomalous diffusion models and their properties BT - non-stationarity, non-ergodicity, and ageing at the centenary of single particle tracking JF - physical chemistry, chemical physics : PCCP N2 - Modern microscopic techniques following the stochastic motion of labelled tracer particles have uncovered significant deviations from the laws of Brownian motion in a variety of animate and inanimate systems. Such anomalous diffusion can have different physical origins, which can be identified from careful data analysis. In particular, single particle tracking provides the entire trajectory of the traced particle, which allows one to evaluate different observables to quantify the dynamics of the system under observation. We here provide an extensive overview over different popular anomalous diffusion models and their properties. We pay special attention to their ergodic properties, highlighting the fact that in several of these models the long time averaged mean squared displacement shows a distinct disparity to the regular, ensemble averaged mean squared displacement. In these cases, data obtained from time averages cannot be interpreted by the standard theoretical results for the ensemble averages. Here we therefore provide a comparison of the main properties of the time averaged mean squared displacement and its statistical behaviour in terms of the scatter of the amplitudes between the time averages obtained from different trajectories. We especially demonstrate how anomalous dynamics may be identified for systems, which, on first sight, appear to be Brownian. Moreover, we discuss the ergodicity breaking parameters for the different anomalous stochastic processes and showcase the physical origins for the various behaviours. This Perspective is intended as a guidebook for both experimentalists and theorists working on systems, which exhibit anomalous diffusion. KW - intermittent chaotic systems KW - Fokker-Planck equations KW - time random-walks KW - fluorescence photobleaching recovery KW - fluctuation-dissipation theorem KW - fractional dynamics approach KW - photon-counting statistics KW - weak ergodicity breaking KW - flight search patterns KW - levy flights Y1 - 2014 U6 - https://doi.org/10.1039/c4cp03465a SN - 1463-9076 SN - 1463-9084 VL - 2014 IS - 16 SP - 24128 EP - 24164 ER - TY - GEN A1 - Metzler, Ralf A1 - Jeon, Jae-Hyung A1 - Cherstvy, Andrey G. A1 - Barkai, Eli T1 - Anomalous diffusion models and their properties BT - non-stationarity, non-ergodicity, and ageing at the centenary of single particle tracking N2 - Modern microscopic techniques following the stochastic motion of labelled tracer particles have uncovered significant deviations from the laws of Brownian motion in a variety of animate and inanimate systems. Such anomalous diffusion can have different physical origins, which can be identified from careful data analysis. In particular, single particle tracking provides the entire trajectory of the traced particle, which allows one to evaluate different observables to quantify the dynamics of the system under observation. We here provide an extensive overview over different popular anomalous diffusion models and their properties. We pay special attention to their ergodic properties, highlighting the fact that in several of these models the long time averaged mean squared displacement shows a distinct disparity to the regular, ensemble averaged mean squared displacement. In these cases, data obtained from time averages cannot be interpreted by the standard theoretical results for the ensemble averages. Here we therefore provide a comparison of the main properties of the time averaged mean squared displacement and its statistical behaviour in terms of the scatter of the amplitudes between the time averages obtained from different trajectories. We especially demonstrate how anomalous dynamics may be identified for systems, which, on first sight, appear to be Brownian. Moreover, we discuss the ergodicity breaking parameters for the different anomalous stochastic processes and showcase the physical origins for the various behaviours. This Perspective is intended as a guidebook for both experimentalists and theorists working on systems, which exhibit anomalous diffusion. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - paper 174 KW - Fokker-Planck equations KW - flight search patterns KW - fluctuation-dissipation theorem KW - fluorescence photobleaching recovery KW - fractional dynamics approach KW - intermittent chaotic systems KW - levy flights KW - photon-counting statistics KW - time random-walks KW - weak ergodicity breaking Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-74448 SP - 24128 EP - 24164 ER - TY - JOUR A1 - Metzler, Ralf A1 - Jeon, Jae-Hyung A1 - Cherstvy, Andrey G. A1 - Barkai, Eli T1 - Anomalous diffusion models and their properties: non-stationarity, non-ergodicity, and ageing at the centenary of single particle tracking JF - Physical chemistry, chemical physics : a journal of European Chemical Societies N2 - Modern microscopic techniques following the stochastic motion of labelled tracer particles have uncovered significant deviations from the laws of Brownian motion in a variety of animate and inanimate systems. Such anomalous diffusion can have different physical origins, which can be identified from careful data analysis. In particular, single particle tracking provides the entire trajectory of the traced particle, which allows one to evaluate different observables to quantify the dynamics of the system under observation. We here provide an extensive overview over different popular anomalous diffusion models and their properties. We pay special attention to their ergodic properties, highlighting the fact that in several of these models the long time averaged mean squared displacement shows a distinct disparity to the regular, ensemble averaged mean squared displacement. In these cases, data obtained from time averages cannot be interpreted by the standard theoretical results for the ensemble averages. Here we therefore provide a comparison of the main properties of the time averaged mean squared displacement and its statistical behaviour in terms of the scatter of the amplitudes between the time averages obtained from different trajectories. We especially demonstrate how anomalous dynamics may be identified for systems, which, on first sight, appear to be Brownian. Moreover, we discuss the ergodicity breaking parameters for the different anomalous stochastic processes and showcase the physical origins for the various behaviours. This Perspective is intended as a guidebook for both experimentalists and theorists working on systems, which exhibit anomalous diffusion. Y1 - 2014 U6 - https://doi.org/10.1039/c4cp03465a SN - 1463-9076 SN - 1463-9084 VL - 16 IS - 44 SP - 24128 EP - 24164 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 - Wang, Wei A1 - Metzler, Ralf A1 - Cherstvy, Andrey G. T1 - Anomalous diffusion, aging, and nonergodicity of scaled Brownian motion with fractional Gaussian noise: overview of related experimental observations and models JF - Physical chemistry, chemical physics : PCCP ; a journal of European chemical societies N2 - How does a systematic time-dependence of the diffusion coefficient D(t) affect the ergodic and statistical characteristics of fractional Brownian motion (FBM)? Here, we answer this question via studying the characteristics of a set of standard statistical quantifiers relevant to single-particle-tracking (SPT) experiments. We examine, for instance, how the behavior of the ensemble- and time-averaged mean-squared displacements-denoted as the standard MSD < x(2)(Delta)> and TAMSD <<(delta(2)(Delta))over bar>> quantifiers-of FBM featuring < x(2) (Delta >> = <<(delta(2)(Delta >)over bar>> proportional to Delta(2H) (where H is the Hurst exponent and Delta is the [lag] time) changes in the presence of a power-law deterministically varying diffusivity D-proportional to(t) proportional to t(alpha-1) -germane to the process of scaled Brownian motion (SBM)-determining the strength of fractional Gaussian noise. The resulting compound "scaled-fractional" Brownian motion or FBM-SBM is found to be nonergodic, with < x(2)(Delta >> proportional to Delta(alpha+)(2H)(-1) and <(delta 2(Delta >) over bar > proportional to Delta(2H). We also detect a stalling behavior of the MSDs for very subdiffusive SBM and FBM, when alpha + 2H - 1 < 0. The distribution of particle displacements for FBM-SBM remains Gaussian, as that for the parent processes of FBM and SBM, in the entire region of scaling exponents (0 < alpha < 2 and 0 < H < 1). The FBM-SBM process is aging in a manner similar to SBM. The velocity autocorrelation function (ACF) of particle increments of FBM-SBM exhibits a dip when the parent FBM process is subdiffusive. Both for sub- and superdiffusive FBM contributions to the FBM-SBM process, the SBM exponent affects the long-time decay exponent of the ACF. Applications of the FBM-SBM-amalgamated process to the analysis of SPT data are discussed. A comparative tabulated overview of recent experimental (mainly SPT) and computational datasets amenable for interpretation in terms of FBM-, SBM-, and FBM-SBM-like models of diffusion culminates the presentation. The statistical aspects of the dynamics of a wide range of biological systems is compared in the table, from nanosized beads in living cells, to chromosomal loci, to water diffusion in the brain, and, finally, to patterns of animal movements. Y1 - 2022 U6 - https://doi.org/10.1039/d2cp01741e SN - 1463-9076 SN - 1463-9084 VL - 24 IS - 31 SP - 18482 EP - 18504 PB - RSC Publ. CY - Cambridge ER - TY - JOUR A1 - Cherstvy, Andrey G. A1 - Safdari, Hadiseh A1 - Metzler, Ralf T1 - Anomalous diffusion, nonergodicity, and ageing for exponentially and logarithmically time-dependent diffusivity BT - striking differences for massive versus massless particles JF - Journal of physics. D, Applied physics N2 - We investigate a diffusion process with a time-dependent diffusion coefficient, both exponentially increasing and decreasing in time, D(t)=D-0(e +/- 2 alpha t). For this (hypothetical) nonstationary diffusion process we compute-both analytically and from extensive stochastic simulations-the behavior of the ensemble- and time-averaged mean-squared displacements (MSDs) of the particles, both in the over- and underdamped limits. Simple asymptotic relations derived for the short- and long-time behaviors are shown to be in excellent agreement with the results of simulations. The diffusive characteristics in the presence of ageing are also considered, with dramatic differences of the over- versus underdamped regime. Our results for D(t)=D-0(e +/- 2 alpha t) extend and generalize the class of diffusive systems obeying scaled Brownian motion featuring a power-law-like variation of the diffusivity with time, D(t) similar to t(alpha-1). We also examine the logarithmically increasing diffusivity, D(t)=D(0)log[t/tau(0)], as another fundamental functional dependence (in addition to the power-law and exponential) and as an example of diffusivity slowly varying in time. One of the main conclusions is that the behavior of the massive particles is predominantly ergodic, while weak ergodicity breaking is repeatedly found for the time-dependent diffusion of the massless particles at short times. The latter manifests itself in the nonequivalence of the (both nonaged and aged) MSD and the mean time-averaged MSD. The current findings are potentially applicable to a class of physical systems out of thermal equilibrium where a rapid increase or decrease of the particles' diffusivity is inherently realized. One biological system potentially featuring all three types of time-dependent diffusion (power-law-like, exponential, and logarithmic) is water diffusion in the brain tissues, as we thoroughly discuss in the end. KW - anomalous diffusion KW - scaled Brownian motion KW - stochastic processes KW - nonstationary diffusivity KW - water diffusion in the brain KW - nonergodicity Y1 - 2021 U6 - https://doi.org/10.1088/1361-6463/abdff0 SN - 0022-3727 SN - 1361-6463 VL - 54 IS - 19 PB - IOP Publ. Ltd. CY - Bristol 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 - Ghosh, Surya K. A1 - Cherstvy, Andrey G. A1 - Grebenkov, Denis S. A1 - Metzler, Ralf T1 - Anomalous, non-Gaussian tracer diffusion in crowded two-dimensional environments JF - NEW JOURNAL OF PHYSICS N2 - A topic of intense current investigation pursues the question of how the highly crowded environment of biological cells affects the dynamic properties of passively diffusing particles. Motivated by recent experiments we report results of extensive simulations of the motion of a finite sized tracer particle in a heterogeneously crowded environment made up of quenched distributions of monodisperse crowders of varying sizes in finite circular two-dimensional domains. For given spatial distributions of monodisperse crowders we demonstrate how anomalous diffusion with strongly non-Gaussian features arises in this model system. We investigate both biologically relevant situations of particles released either at the surface of an inner domain or at the outer boundary, exhibiting distinctly different features of the observed anomalous diffusion for heterogeneous distributions of crowders. Specifically we reveal an asymmetric spreading of tracers even at moderate crowding. In addition to the mean squared displacement (MSD) and local diffusion exponent we investigate the magnitude and the amplitude scatter of the time averaged MSD of individual tracer trajectories, the non-Gaussianity parameter, and the van Hove correlation function. We also quantify how the average tracer diffusivity varies with the position in the domain with a heterogeneous radial distribution of crowders and examine the behaviour of the survival probability and the dynamics of the tracer survival probability. Inter alia, the systems we investigate are related to the passive transport of lipid molecules and proteins in two-dimensional crowded membranes or the motion in colloidal solutions or emulsions in effectively two-dimensional geometries, as well as inside supercrowded, surface adhered cells. KW - anomalous diffusion KW - crowded fluids KW - stochastic processes Y1 - 2016 U6 - https://doi.org/10.1088/1367-2630/18/1/013027 SN - 1367-2630 VL - 18 PB - IOP Publ. Ltd. CY - Bristol ER - TY - JOUR A1 - Doerries, Timo J. A1 - Chechkin, Aleksei V. A1 - Metzler, Ralf T1 - Apparent anomalous diffusion and non-Gaussian distributions in a simple mobile-immobile transport model with Poissonian switching JF - Interface : journal of the Royal Society N2 - We analyse mobile-immobile transport of particles that switch between the mobile and immobile phases with finite rates. Despite this seemingly simple assumption of Poissonian switching, we unveil a rich transport dynamics including significant transient anomalous diffusion and non-Gaussian displacement distributions. Our discussion is based on experimental parameters for tau proteins in neuronal cells, but the results obtained here are expected to be of relevance for a broad class of processes in complex systems. Specifically, we obtain that, when the mean binding time is significantly longer than the mean mobile time, transient anomalous diffusion is observed at short and intermediate time scales, with a strong dependence on the fraction of initially mobile and immobile particles. We unveil a Laplace distribution of particle displacements at relevant intermediate time scales. For any initial fraction of mobile particles, the respective mean squared displacement (MSD) displays a plateau. Moreover, we demonstrate a short-time cubic time dependence of the MSD for immobile tracers when initially all particles are immobile. KW - diffusion KW - mobile-immobile model KW - tau proteins Y1 - 2022 U6 - https://doi.org/10.1098/rsif.2022.0233 SN - 1742-5689 SN - 1742-5662 VL - 19 IS - 192 PB - Royal Society CY - London 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 - Padash, Amin A1 - Sandev, Trifce A1 - Kantz, Holger A1 - Metzler, Ralf A1 - Chechkin, Aleksei T1 - Asymmetric Levy flights are more efficient in random search JF - Fractal and fractional N2 - We study the first-arrival (first-hitting) dynamics and efficiency of a one-dimensional random search model performing asymmetric Levy flights by leveraging the Fokker-Planck equation with a delta-sink and an asymmetric space-fractional derivative operator with stable index alpha and asymmetry (skewness) parameter beta. We find exact analytical results for the probability density of first-arrival times and the search efficiency, and we analyse their behaviour within the limits of short and long times. We find that when the starting point of the searcher is to the right of the target, random search by Brownian motion is more efficient than Levy flights with beta <= 0 (with a rightward bias) for short initial distances, while for beta>0 (with a leftward bias) Levy flights with alpha -> 1 are more efficient. When increasing the initial distance of the searcher to the target, Levy flight search (except for alpha=1 with beta=0) is more efficient than the Brownian search. Moreover, the asymmetry in jumps leads to essentially higher efficiency of the Levy search compared to symmetric Levy flights at both short and long distances, and the effect is more pronounced for stable indices alpha close to unity. KW - asymmetric Levy flights KW - first-arrival density KW - search efficiency Y1 - 2022 U6 - https://doi.org/10.3390/fractalfract6050260 SN - 2504-3110 VL - 6 IS - 5 PB - MDPI CY - Basel ER - TY - JOUR A1 - Thapa, Samudrajit A1 - Lomholt, Michael Andersen A1 - Krog, Jens A1 - Cherstvy, Andrey G. A1 - Metzler, Ralf T1 - Bayesian analysis of single-particle tracking data using the nested-sampling algorithm: maximum-likelihood model selection applied to stochastic-diffusivity data JF - Physical chemistry, chemical physics : PCCP ; a journal of European Chemical Societies N2 - We employ Bayesian statistics using the nested-sampling algorithm to compare and rank multiple models of ergodic diffusion (including anomalous diffusion) as well as to assess their optimal parameters for in silico-generated and real time-series. We focus on the recently-introduced model of Brownian motion with "diffusing diffusivity'-giving rise to widely-observed non-Gaussian displacement statistics-and its comparison to Brownian and fractional Brownian motion, also for the time-series with some measurement noise. We conduct this model-assessment analysis using Bayesian statistics and the nested-sampling algorithm on the level of individual particle trajectories. We evaluate relative model probabilities and compute best-parameter sets for each diffusion model, comparing the estimated parameters to the true ones. We test the performance of the nested-sampling algorithm and its predictive power both for computer-generated (idealised) trajectories as well as for real single-particle-tracking trajectories. Our approach delivers new important insight into the objective selection of the most suitable stochastic model for a given time-series. We also present first model-ranking results in application to experimental data of tracer diffusion in polymer-based hydrogels. Y1 - 2018 U6 - https://doi.org/10.1039/c8cp04043e SN - 1463-9076 SN - 1463-9084 VL - 20 IS - 46 SP - 29018 EP - 29037 PB - Royal Society of Chemistry CY - Cambridge ER - TY - JOUR A1 - Seckler, Henrik A1 - Metzler, Ralf T1 - Bayesian deep learning for error estimation in the analysis of anomalous diffusion JF - Nature Communnications N2 - Modern single-particle-tracking techniques produce extensive time-series of diffusive motion in a wide variety of systems, from single-molecule motion in living-cells to movement ecology. The quest is to decipher the physical mechanisms encoded in the data and thus to better understand the probed systems. We here augment recently proposed machine-learning techniques for decoding anomalous-diffusion data to include an uncertainty estimate in addition to the predicted output. To avoid the Black-Box-Problem a Bayesian-Deep-Learning technique named Stochastic-Weight-Averaging-Gaussian is used to train models for both the classification of the diffusionmodel and the regression of the anomalous diffusion exponent of single-particle-trajectories. Evaluating their performance, we find that these models can achieve a wellcalibrated error estimate while maintaining high prediction accuracies. In the analysis of the output uncertainty predictions we relate these to properties of the underlying diffusion models, thus providing insights into the learning process of the machine and the relevance of the output. KW - random-walk KW - models Y1 - 2022 U6 - https://doi.org/10.1038/s41467-022-34305-6 SN - 2041-1723 VL - 13 PB - Nature Publishing Group UK CY - London ER - TY - JOUR A1 - Seckler, Henrik A1 - Metzler, Ralf T1 - Bayesian deep learning for error estimation in the analysis of anomalous diffusion JF - Nature Communications N2 - Modern single-particle-tracking techniques produce extensive time-series of diffusive motion in a wide variety of systems, from single-molecule motion in living-cells to movement ecology. The quest is to decipher the physical mechanisms encoded in the data and thus to better understand the probed systems. We here augment recently proposed machine-learning techniques for decoding anomalous-diffusion data to include an uncertainty estimate in addition to the predicted output. To avoid the Black-Box-Problem a Bayesian-Deep-Learning technique named Stochastic-Weight-Averaging-Gaussian is used to train models for both the classification of the diffusion model and the regression of the anomalous diffusion exponent of single-particle-trajectories. Evaluating their performance, we find that these models can achieve a well-calibrated error estimate while maintaining high prediction accuracies. In the analysis of the output uncertainty predictions we relate these to properties of the underlying diffusion models, thus providing insights into the learning process of the machine and the relevance of the output.
Diffusive motions in complex environments such as living biological cells or soft matter systems can be analyzed with single-particle-tracking approaches, where accuracy of output may vary. The authors involve a machine-learning technique for decoding anomalous-diffusion data and provide an uncertainty estimate together with predicted output. Y1 - 2022 U6 - https://doi.org/10.1038/s41467-022-34305-6 SN - 2041-1723 VL - 13 IS - 1 PB - Nature portfolio CY - Berlin ER - TY - GEN A1 - Seckler, Henrik A1 - Metzler, Ralf T1 - Bayesian deep learning for error estimation in the analysis of anomalous diffusion T2 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe N2 - Sprache Englisch Modern single-particle-tracking techniques produce extensive time-series of diffusive motion in a wide variety of systems, from single-molecule motion in living-cells to movement ecology. The quest is to decipher the physical mechanisms encoded in the data and thus to better understand the probed systems. We here augment recently proposed machine-learning techniques for decoding anomalous-diffusion data to include an uncertainty estimate in addition to the predicted output. To avoid the Black-Box-Problem a Bayesian-Deep-Learning technique named Stochastic-Weight-Averaging-Gaussian is used to train models for both the classification of the diffusionmodel and the regression of the anomalous diffusion exponent of single-particle-trajectories. Evaluating their performance, we find that these models can achieve a wellcalibrated error estimate while maintaining high prediction accuracies. In the analysis of the output uncertainty predictions we relate these to properties of the underlying diffusion models, thus providing insights into the learning process of the machine and the relevance of the output. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 1314 KW - random-walk KW - models Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-586025 SN - 1866-8372 IS - 1314 ER - TY - JOUR A1 - Thapa, Samudrajit A1 - Park, Seongyu A1 - Kim, Yeongjin A1 - Jeon, Jae-Hyung A1 - Metzler, Ralf A1 - Lomholt, Michael A. T1 - Bayesian inference of scaled versus fractional Brownian motion JF - Journal of physics : A, mathematical and theoretical N2 - We present a Bayesian inference scheme for scaled Brownian motion, and investigate its performance on synthetic data for parameter estimation and model selection in a combined inference with fractional Brownian motion. We include the possibility of measurement noise in both models. We find that for trajectories of a few hundred time points the procedure is able to resolve well the true model and parameters. Using the prior of the synthetic data generation process also for the inference, the approach is optimal based on decision theory. We include a comparison with inference using a prior different from the data generating one. KW - Bayesian inference KW - scaled Brownian motion KW - single particle tracking Y1 - 2022 U6 - https://doi.org/10.1088/1751-8121/ac60e7 SN - 1751-8113 SN - 1751-8121 VL - 55 IS - 19 PB - IOP Publ. Ltd. CY - Bristol ER - TY - JOUR A1 - Sandev, Trifce A1 - Sokolov, Igor M. A1 - Metzler, Ralf A1 - Chechkin, Aleksei V. T1 - Beyond monofractional kinetics JF - Chaos, solitons & fractals : applications in science and engineering ; an interdisciplinary journal of nonlinear science N2 - We discuss generalized integro-differential diffusion equations whose integral kernels are not of a simple power law form, and thus these equations themselves do not belong to the family of fractional diffusion equations exhibiting a monoscaling behavior. They instead generate a broad class of anomalous nonscaling patterns, which correspond either to crossovers between different power laws, or to a non-power-law behavior as exemplified by the logarithmic growth of the width of the distribution. We consider normal and modified forms of these generalized diffusion equations and provide a brief discussion of three generic types of integral kernels for each form, namely, distributed order, truncated power law and truncated distributed order kernels. For each of the cases considered we prove the non-negativity of the solution of the corresponding generalized diffusion equation and calculate the mean squared displacement. (C) 2017 Elsevier Ltd. All rights reserved. KW - Distributed order diffusion-wave equations KW - Complete Bernstein function KW - Completely monotone function Y1 - 2017 U6 - https://doi.org/10.1016/j.chaos.2017.05.001 SN - 0960-0779 SN - 1873-2887 VL - 102 SP - 210 EP - 217 PB - Elsevier CY - Oxford ER - TY - JOUR A1 - Hou, Ru A1 - Cherstvy, Andrey G. A1 - Metzler, Ralf A1 - Akimoto, Takuma T1 - Biased continuous-time random walks for ordinary and equilibrium cases BT - facilitation of diffusion, ergodicity breaking and ageing JF - Physical chemistry, chemical physics : a journal of European Chemical Societies N2 - We examine renewal processes with power-law waiting time distributions (WTDs) and non-zero drift via computing analytically and by computer simulations their ensemble and time averaged spreading characteristics. All possible values of the scaling exponent alpha are considered for the WTD psi(t) similar to 1/t(1+alpha). We treat continuous-time random walks (CTRWs) with 0 < alpha < 1 for which the mean waiting time diverges, and investigate the behaviour of the process for both ordinary and equilibrium CTRWs for 1 < alpha < 2 and alpha > 2. We demonstrate that in the presence of a drift CTRWs with alpha < 1 are ageing and non-ergodic in the sense of the non-equivalence of their ensemble and time averaged displacement characteristics in the limit of lag times much shorter than the trajectory length. In the sense of the equivalence of ensemble and time averages, CTRW processes with 1 < alpha < 2 are ergodic for the equilibrium and non-ergodic for the ordinary situation. Lastly, CTRW renewal processes with alpha > 2-both for the equilibrium and ordinary situation-are always ergodic. For the situations 1 < alpha < 2 and alpha > 2 the variance of the diffusion process, however, depends on the initial ensemble. For biased CTRWs with alpha > 1 we also investigate the behaviour of the ergodicity breaking parameter. In addition, we demonstrate that for biased CTRWs the Einstein relation is valid on the level of the ensemble and time averaged displacements, in the entire range of the WTD exponent alpha. Y1 - 2018 U6 - https://doi.org/10.1039/c8cp01863d SN - 1463-9076 SN - 1463-9084 VL - 20 IS - 32 SP - 20827 EP - 20848 PB - Royal Society of Chemistry CY - Cambridge 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 - GEN 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 T2 - 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. Y1 - 2014 U6 - https://doi.org/10.1063/1.4871297 SN - 0021-9606 SN - 1089-7690 VL - 140 IS - 14 PB - American Institute of Physics CY - Melville ER - TY - JOUR A1 - Metzler, Ralf T1 - Brownian motion and beyond: first-passage, power spectrum, non-Gaussianity, and anomalous diffusion JF - Journal of statistical mechanics: theory and experiment N2 - Brownian motion is a ubiquitous physical phenomenon across the sciences. After its discovery by Brown and intensive study since the first half of the 20th century, many different aspects of Brownian motion and stochastic processes in general have been addressed in Statistical Physics. In particular, there now exists a very large range of applications of stochastic processes in various disciplines. Here we provide a summary of some of the recent developments in the field of stochastic processes, highlighting both the experimental findings and theoretical frameworks. KW - 15 KW - 4 Y1 - 2019 U6 - https://doi.org/10.1088/1742-5468/ab4988 SN - 1742-5468 VL - 2019 IS - 11 PB - IOP Publ. Ltd. CY - Bristol ER - TY - JOUR A1 - Chechkin, Aleksei V. A1 - Seno, Flavio A1 - Metzler, Ralf A1 - Sokolov, Igor M. T1 - Brownian yet Non-Gaussian Diffusion: From Superstatistics to Subordination of Diffusing Diffusivities JF - Physical review : X, Expanding access N2 - A growing number of biological, soft, and active matter systems are observed to exhibit normal diffusive dynamics with a linear growth of the mean-squared displacement, yet with a non-Gaussian distribution of increments. Based on the Chubinsky-Slater idea of a diffusing diffusivity, we here establish and analyze a minimal model framework of diffusion processes with fluctuating diffusivity. In particular, we demonstrate the equivalence of the diffusing diffusivity process with a superstatistical approach with a distribution of diffusivities, at times shorter than the diffusivity correlation time. At longer times, a crossover to a Gaussian distribution with an effective diffusivity emerges. Specifically, we establish a subordination picture of Brownian but non-Gaussian diffusion processes, which can be used for a wide class of diffusivity fluctuation statistics. Our results are shown to be in excellent agreement with simulations and numerical evaluations. Y1 - 2017 U6 - https://doi.org/10.1103/PhysRevX.7.021002 SN - 2160-3308 VL - 7 PB - American Physical Society CY - College Park ER - TY - JOUR A1 - Emanuel, Marc D. A1 - Cherstvy, Andrey G. A1 - Metzler, Ralf A1 - Gompper, Gerhard T1 - Buckling transitions and soft-phase invasion of two-component icosahedral shells JF - Physical review / publ. by The American Physical Society. E, Statistical, nonlinear, and soft matter physics N2 - What is the optimal distribution of two types of crystalline phases on the surface of icosahedral shells, such as of many viral capsids? We here investigate the distribution of a thin layer of soft material on a crystalline convex icosahedral shell. We demonstrate how the shapes of spherical viruses can be understood from the perspective of elasticity theory of thin two-component shells. We develop a theory of shape transformations of an icosahedral shell upon addition of a softer, but still crystalline, material onto its surface. We show how the soft component "invades" the regions with the highest elastic energy and stress imposed by the 12 topological defects on the surface. We explore the phase diagram as a function of the surface fraction of the soft material, the shell size, and the incommensurability of the elastic moduli of the rigid and soft phases. We find that, as expected, progressive filling of the rigid shell by the soft phase starts from the most deformed regions of the icosahedron. With a progressively increasing soft-phase coverage, the spherical segments of domes are filled first (12 vertices of the shell), then the cylindrical segments connecting the domes (30 edges) are invaded, and, ultimately, the 20 flat faces of the icosahedral shell tend to be occupied by the soft material. We present a detailed theoretical investigation of the first two stages of this invasion process and develop a model of morphological changes of the cone structure that permits noncircular cross sections. In conclusion, we discuss the biological relevance of some structures predicted from our calculations, in particular for the shape of viral capsids. Y1 - 2020 U6 - https://doi.org/10.1103/PhysRevE.102.062104 SN - 2470-0045 SN - 2470-0053 SN - 2470-0061 SN - 1538-4519 VL - 102 IS - 6 PB - Woodbury CY - New York ER -