TY - JOUR A1 - Grebenkov, Denis S. A1 - Metzler, Ralf A1 - Oshanin, Gleb T1 - Search efficiency in the Adam-Delbruck reduction-of-dimensionality scenario versus direct diffusive search JF - New journal of physics : the open-access journal for physics N2 - The time instant-the first-passage time (FPT)-when a diffusive particle (e.g., a ligand such as oxygen or a signalling protein) for the first time reaches an immobile target located on the surface of a bounded three-dimensional domain (e.g., a hemoglobin molecule or the cellular nucleus) is a decisive characteristic time-scale in diverse biophysical and biochemical processes, as well as in intermediate stages of various inter- and intra-cellular signal transduction pathways. Adam and Delbruck put forth the reduction-of-dimensionality concept, according to which a ligand first binds non-specifically to any point of the surface on which the target is placed and then diffuses along this surface until it locates the target. In this work, we analyse the efficiency of such a scenario and confront it with the efficiency of a direct search process, in which the target is approached directly from the bulk and not aided by surface diffusion. We consider two situations: (i) a single ligand is launched from a fixed or a random position and searches for the target, and (ii) the case of 'amplified' signals when N ligands start either from the same point or from random positions, and the search terminates when the fastest of them arrives to the target. For such settings, we go beyond the conventional analyses, which compare only the mean values of the corresponding FPTs. Instead, we calculate the full probability density function of FPTs for both scenarios and study its integral characteristic-the 'survival' probability of a target up to time t. On this basis, we examine how the efficiencies of both scenarios are controlled by a variety of parameters and single out realistic conditions in which the reduction-of-dimensionality scenario outperforms the direct search. KW - first-passage times KW - Adam-Delbruck scenario KW - dimensional reduction KW - bulk KW - and surface diffusion Y1 - 2022 U6 - https://doi.org/10.1088/1367-2630/ac8824 SN - 1367-2630 VL - 24 IS - 8 PB - IOP Publ. Ltd. CY - Bristol ER - TY - JOUR A1 - Sposini, Vittoria A1 - Metzler, Ralf A1 - Oshanin, Gleb T1 - Single-trajectory spectral analysis of scaled Brownian motion JF - New Journal of Physics N2 - Astandard approach to study time-dependent stochastic processes is the power spectral density (PSD), an ensemble-averaged property defined as the Fourier transform of the autocorrelation function of the process in the asymptotic limit of long observation times, T → ∞. In many experimental situations one is able to garner only relatively few stochastic time series of finite T, such that practically neither an ensemble average nor the asymptotic limit T → ∞ can be achieved. To accommodate for a meaningful analysis of such finite-length data we here develop the framework of single-trajectory spectral analysis for one of the standard models of anomalous diffusion, scaled Brownian motion.Wedemonstrate that the frequency dependence of the single-trajectory PSD is exactly the same as for standard Brownian motion, which may lead one to the erroneous conclusion that the observed motion is normal-diffusive. However, a distinctive feature is shown to be provided by the explicit dependence on the measurement time T, and this ageing phenomenon can be used to deduce the anomalous diffusion exponent.Wealso compare our results to the single-trajectory PSD behaviour of another standard anomalous diffusion process, fractional Brownian motion, and work out the commonalities and differences. Our results represent an important step in establishing singletrajectory PSDs as an alternative (or complement) to analyses based on the time-averaged mean squared displacement. KW - diffusion KW - anomalous diffusion KW - power spectral analysis KW - single trajectory analysis Y1 - 2019 U6 - https://doi.org/10.1088/1367-2630/ab2f52 SN - 1367-2630 VL - 21 PB - Deutsche Physikalische Gesellschaft ; IOP, Institute of Physics CY - Bad Honnef und London ER - TY - JOUR A1 - Krapf, Diego A1 - Lukat, Nils A1 - Marinari, Enzo A1 - Metzler, Ralf A1 - Oshanin, Gleb A1 - Selhuber-Unkel, Christine A1 - Squarcini, Alessio A1 - Stadler, Lorenz A1 - Weiss, Matthias A1 - Xu, Xinran T1 - Spectral Content of a Single Non-Brownian Trajectory JF - Physical review : X, Expanding access N2 - Time-dependent processes are often analyzed using the power spectral density (PSD) calculated by taking an appropriate Fourier transform of individual trajectories and finding the associated ensemble average. Frequently, the available experimental datasets are too small for such ensemble averages, and hence, it is of a great conceptual and practical importance to understand to which extent relevant information can be gained from S(f, T), the PSD of a single trajectory. Here we focus on the behavior of this random, realization-dependent variable parametrized by frequency f and observation time T, for a broad family of anomalous diffusions-fractional Brownian motion with Hurst index H-and derive exactly its probability density function. We show that S(f, T) is proportional-up to a random numerical factor whose universal distribution we determine-to the ensemble-averaged PSD. For subdiffusion (H < 1/2), we find that S(f, T) similar to A/f(2H+1) with random amplitude A. In sharp contrast, for superdiffusion (H > 1/2) S(f, T) similar to BT2H-1/f(2) with random amplitude B. Remarkably, for H > 1/2 the PSD exhibits the same frequency dependence as Brownian motion, a deceptive property that may lead to false conclusions when interpreting experimental data. Notably, for H > 1/2 the PSD is ageing and is dependent on T. Our predictions for both sub-and superdiffusion are confirmed by experiments in live cells and in agarose hydrogels and by extensive simulations. KW - Biological Physics KW - Interdisciplinary Physics KW - Statistical Physics Y1 - 2019 U6 - https://doi.org/10.1103/PhysRevX.9.011019 SN - 2160-3308 VL - 9 IS - 1 PB - American Physical Society CY - College Park ER - TY - JOUR A1 - Grebenkov, Denis S. A1 - Metzler, Ralf A1 - Oshanin, Gleb T1 - Strong defocusing of molecular reaction times results from an interplay of geometry and reaction control JF - Communications Chemistry N2 - Textbook concepts of diffusion-versus kinetic-control are well-defined for reaction-kinetics involving macroscopic concentrations of diffusive reactants that are adequately described by rate-constants—the inverse of the mean-first-passage-time to the reaction-event. In contradiction, an open important question is whether the mean-first-passage-time alone is a sufficient measure for biochemical reactions that involve nanomolar reactant concentrations. Here, using a simple yet generic, exactly solvable model we study the effect of diffusion and chemical reaction-limitations on the full reaction-time distribution. We show that it has a complex structure with four distinct regimes delineated by three characteristic time scales spanning a window of several decades. Consequently, the reaction-times are defocused: no unique time-scale characterises the reaction-process, diffusion- and kinetic-control can no longer be disentangled, and it is imperative to know the full reaction-time distribution. We introduce the concepts of geometry- and reaction-control, and also quantify each regime by calculating the corresponding reaction depth. Y1 - 2018 U6 - https://doi.org/10.1038/s42004-018-0096-x SN - 2399-3669 VL - 1 PB - Macmillan Publishers Limited CY - London ER - TY - JOUR A1 - Grebenkov, Denis S. A1 - Metzler, Ralf A1 - Oshanin, Gleb T1 - Towards a full quantitative description of single-molecule reaction kinetics in biological cells JF - Physical chemistry, chemical physics : a journal of European Chemical Societies N2 - The first-passage time (FPT), i.e., the moment when a stochastic process reaches a given threshold value for the first time, is a fundamental mathematical concept with immediate applications. In particular, it quantifies the statistics of instances when biomolecules in a biological cell reach their specific binding sites and trigger cellular regulation. Typically, the first-passage properties are given in terms of mean first-passage times. However, modern experiments now monitor single-molecular binding-processes in living cells and thus provide access to the full statistics of the underlying first-passage events, in particular, inherent cell-to-cell fluctuations. We here present a robust explicit approach for obtaining the distribution of FPTs to a small partially reactive target in cylindrical-annulus domains, which represent typical bacterial and neuronal cell shapes. We investigate various asymptotic behaviours of this FPT distribution and show that it is typically very broad in many biological situations, thus, the mean FPT can differ from the most probable FPT by orders of magnitude. The most probable FPT is shown to strongly depend only on the starting position within the geometry and to be almost independent of the target size and reactivity. These findings demonstrate the dramatic relevance of knowing the full distribution of FPTs and thus open new perspectives for a more reliable description of many intracellular processes initiated by the arrival of one or few biomolecules to a small, spatially localised region inside the cell. Y1 - 2018 U6 - https://doi.org/10.1039/c8cp02043d SN - 1463-9076 SN - 1463-9084 VL - 20 IS - 24 SP - 16393 EP - 16401 PB - Royal Society of Chemistry CY - Cambridge ER - TY - JOUR A1 - Sposini, Vittoria A1 - Krapf, Diego A1 - Marinari, Enzo A1 - Sunyer, Raimon A1 - Ritort, Felix A1 - Taheri, Fereydoon A1 - Selhuber-Unkel, Christine A1 - Benelli, Rebecca A1 - Weiss, Matthias A1 - Metzler, Ralf A1 - Oshanin, Gleb T1 - Towards a robust criterion of anomalous diffusion JF - Communications Physics N2 - Anomalous-diffusion, the departure of the spreading dynamics of diffusing particles from the traditional law of Brownian-motion, is a signature feature of a large number of complex soft-matter and biological systems. Anomalous-diffusion emerges due to a variety of physical mechanisms, e.g., trapping interactions or the viscoelasticity of the environment. However, sometimes systems dynamics are erroneously claimed to be anomalous, despite the fact that the true motion is Brownian—or vice versa. This ambiguity in establishing whether the dynamics as normal or anomalous can have far-reaching consequences, e.g., in predictions for reaction- or relaxation-laws. Demonstrating that a system exhibits normal- or anomalous-diffusion is highly desirable for a vast host of applications. Here, we present a criterion for anomalous-diffusion based on the method of power-spectral analysis of single trajectories. The robustness of this criterion is studied for trajectories of fractional-Brownian-motion, a ubiquitous stochastic process for the description of anomalous-diffusion, in the presence of two types of measurement errors. In particular, we find that our criterion is very robust for subdiffusion. Various tests on surrogate data in absence or presence of additional positional noise demonstrate the efficacy of this method in practical contexts. Finally, we provide a proof-of-concept based on diverse experiments exhibiting both normal and anomalous-diffusion. Y1 - 2022 U6 - https://doi.org/10.1038/s42005-022-01079-8 SN - 2399-3650 VL - 5 PB - Springer Nature CY - London ER - TY - JOUR A1 - Grebenkov, Denis S. A1 - Metzler, Ralf A1 - Oshanin, Gleb A1 - Dagdug, Leonardo A1 - Berezhkovskii, Alexander M. A1 - Skvortsov, Alexei T. T1 - Trapping of diffusing particles by periodic absorbing rings on a cylindrical tube JF - The journal of chemical physics : bridges a gap between journals of physics and journals of chemistr Y1 - 2019 U6 - https://doi.org/10.1063/1.5098390 SN - 0021-9606 SN - 1089-7690 VL - 150 IS - 20 PB - American Institute of Physics CY - Melville ER - TY - JOUR A1 - Sposini, Vittoria A1 - Grebenkov, Denis S. A1 - Metzler, Ralf A1 - Oshanin, Gleb A1 - Seno, Flavio T1 - Universal spectral features of different classes of random-diffusivity processes JF - New Journal of Physics N2 - Stochastic models based on random diffusivities, such as the diffusing-diffusivity approach, are popular concepts for the description of non-Gaussian diffusion in heterogeneous media. Studies of these models typically focus on the moments and the displacement probability density function. Here we develop the complementary power spectral description for a broad class of random-diffusivity processes. In our approach we cater for typical single particle tracking data in which a small number of trajectories with finite duration are garnered. Apart from the diffusing-diffusivity model we study a range of previously unconsidered random-diffusivity processes, for which we obtain exact forms of the probability density function. These new processes are different versions of jump processes as well as functionals of Brownian motion. The resulting behaviour subtly depends on the specific model details. Thus, the central part of the probability density function may be Gaussian or non-Gaussian, and the tails may assume Gaussian, exponential, log-normal, or even power-law forms. For all these models we derive analytically the moment-generating function for the single-trajectory power spectral density. We establish the generic 1/f²-scaling of the power spectral density as function of frequency in all cases. Moreover, we establish the probability density for the amplitudes of the random power spectral density of individual trajectories. The latter functions reflect the very specific properties of the different random-diffusivity models considered here. Our exact results are in excellent agreement with extensive numerical simulations. KW - diffusion KW - power spectrum KW - random diffusivity KW - single trajectories Y1 - 2020 U6 - https://doi.org/10.1088/1367-2630/ab9200 SN - 1367-2630 VL - 22 IS - 6 PB - Dt. Physikalische Ges. CY - Bad Honnef ER -