Signal focusing through active transport

In biological cells and novel diagnostic devices biochemical receptors need to be sensitive to extremely small concentration changes of signaling molecules. The accuracy of such molecular signaling is ultimately limited by the counting noise imposed by the thermal diffusion of molecules. Many macromolecules and organelles transiently bind to molecular motors and are then actively transported. We here show that a random albeit directed delivery of signaling molecules to within a typical diffusion distance to the receptor reduces the correlation time of the counting noise, effecting an improved sensing precision. The conditions for this active focusing are indeed compatible with observations in living cells. Our results are relevant for a better understanding of molecular cellular signaling and the design of novel diagnostic devices.Comment: 5 pages. 3 figures, includes supplementary material (2 pages

Finite-time effects and ultraweak ergodicity breaking in superdiffusive dynamics

We study the ergodic properties of superdiffusive, spatiotemporally coupled Levy walk processes. For trajectories of finite duration, we reveal a distinct scatter of the scaling exponents of the time averaged mean squared displacement delta**2 around the ensemble value 3-alpha (1<alpha<2) ranging from ballistic motion to subdiffusion, in strong contrast to the behavior of subdiffusive processes. In addition we find a significant dependence of the trajectory-to-trajectory average of delta**2 as function of the finite measurement time. This so-called finite-time amplitude depression and the scatter of the scaling exponent is vital in the quantitative evaluation of superdiffusive processes. Comparing the long time average of the second moment with the ensemble mean squared displacement, these only differ by a constant factor, an ultraweak ergodicity breaking.Comment: 5 pages, 4 Figures, REVTe

Optimization and universality of Brownian search in quenched heterogeneous media

The kinetics of a variety of transport-controlled processes can be reduced to the problem of determining the mean time needed to arrive at a given location for the first time, the so called mean first passage time (MFPT) problem. The occurrence of occasional large jumps or intermittent patterns combining various types of motion are known to outperform the standard random walk with respect to the MFPT, by reducing oversampling of space. Here we show that a regular but spatially heterogeneous random walk can significantly and universally enhance the search in any spatial dimension. In a generic minimal model we consider a spherically symmetric system comprising two concentric regions with piece-wise constant diffusivity. The MFPT is analyzed under the constraint of conserved average dynamics, that is, the spatially averaged diffusivity is kept constant. Our analytical calculations and extensive numerical simulations demonstrate the existence of an {\em optimal heterogeneity} minimizing the MFPT to the target. We prove that the MFPT for a random walk is completely dominated by what we term direct trajectories towards the target and reveal a remarkable universality of the spatially heterogeneous search with respect to target size and system dimensionality. In contrast to intermittent strategies, which are most profitable in low spatial dimensions, the spatially inhomogeneous search performs best in higher dimensions. Discussing our results alongside recent experiments on single particle tracking in living cells we argue that the observed spatial heterogeneity may be beneficial for cellular signaling processes.Comment: 19 pages, 11 figures, RevTe

In vivo facilitated diffusion model

Under dilute in vitro conditions transcription factors rapidly locate their target sequence on DNA by using the facilitated diffusion mechanism. However, whether this strategy of alternating between three-dimensional bulk diffusion and one-dimensional sliding along the DNA contour is still beneficial in the crowded interior of cells is highly disputed. Here we use a simple model for the bacterial genome inside the cell and present a semi-analytical model for the in vivo target search of transcription factors within the facilitated diffusion framework. Without having to resort to extensive simulations we determine the mean search time of a lac repressor in a living E. coli cell by including parameters deduced from experimental measurements. The results agree very well with experimental findings, and thus the facilitated diffusion picture emerges as a quantitative approach to gene regulation in living bacteria cells. Furthermore we see that the search time is not very sensitive to the parameters characterizing the DNA configuration and that the cell seems to operate very close to optimal conditions for target localization. Local searches as implied by the colocalization mechanism are only found to mildly accelerate the mean search time within our model.Comment: 19 pages, 9 figures, Supplementary Information directly include