Mean exit time for surface-mediated diffusion: spectral analysis and asymptotic behavior

We consider a model of surface-mediated diffusion with alternating phases of pure bulk and surface diffusion. For this process, we compute the mean exit time from a disk through a hole on the circle. We develop a spectral approach to this escape problem in which the mean exit time is explicitly expressed through the eigenvalues of the related self-adjoint operator. This representation is particularly well suited to investigate the asymptotic behavior of the mean exit time in the limit of large desorption rate $\lambda$. For a point-like target, we show that the mean exit time diverges as $\sqrt{\lambda}$. For extended targets, we establish the asymptotic approach to a finite limit. In both cases, the mean exit time is shown to asymptotically increase as $\lambda$ tends to infinity. We also revise the optimality regime of surface-mediated diffusion. Although the presentation is limited to the unit disk, the spectral approach can be extended to other domains such as rectangles or spheres.Comment: 21 pages, 7 figure

Enhanced reaction kinetics in biological cells

The cell cytoskeleton is a striking example of "active" medium driven out-of-equilibrium by ATP hydrolysis. Such activity has been shown recently to have a spectacular impact on the mechanical and rheological properties of the cellular medium, as well as on its transport properties : a generic tracer particle freely diffuses as in a standard equilibrium medium, but also intermittently binds with random interaction times to motor proteins, which perform active ballistic excursions along cytoskeletal filaments. Here, we propose for the first time an analytical model of transport limited reactions in active media, and show quantitatively how active transport can enhance reactivity for large enough tracers like vesicles. We derive analytically the average interaction time with motor proteins which optimizes the reaction rate, and reveal remarkable universal features of the optimal configuration. We discuss why active transport may be beneficial in various biological examples: cell cytoskeleton, membranes and lamellipodia, and tubular structures like axons.Comment: 10 pages, 2 figure

On the Plants Leaves Boundary, "Jupe \`a Godets" and Conformal Embeddings

The stable profile of the boundary of a plant's leaf fluctuating in the direction transversal to the leaf's surface is described in the framework of a model called a "surface \`a godets". It is shown that the information on the profile is encoded in the Jacobian of a conformal mapping (the coefficient of deformation) corresponding to an isometric embedding of a uniform Cayley tree into the 3D Euclidean space. The geometric characteristics of the leaf's boundary (like the perimeter and the height) are calculated. In addition a symbolic language allowing to investigate statistical properties of a "surface \`a godets" with annealed random defects of curvature of density $q$ is developed. It is found that at $q=1$ the surface exhibits a phase transition with critical exponent $\alpha=1/2$ from the exponentially growing to the flat structure.Comment: 17 pages (revtex), 8 eps-figures, to appear in Journal of Physics

Random walk generated by random permutations of {1,2,3, ..., n+1}

We study properties of a non-Markovian random walk $X^{(n)}_l$, $l =0,1,2, >...,n$, evolving in discrete time $l$ on a one-dimensional lattice of integers, whose moves to the right or to the left are prescribed by the \text{rise-and-descent} sequences characterizing random permutations $\pi$ of $[n+1] = \{1,2,3, ...,n+1\}$. We determine exactly the probability of finding the end-point $X_n = X^{(n)}_n$ of the trajectory of such a permutation-generated random walk (PGRW) at site $X$, and show that in the limit $n \to \infty$ it converges to a normal distribution with a smaller, compared to the conventional P\'olya random walk, diffusion coefficient. We formulate, as well, an auxiliary stochastic process whose distribution is identic to the distribution of the intermediate points $X^{(n)}_l$, $l < n$, which enables us to obtain the probability measure of different excursions and to define the asymptotic distribution of the number of "turns" of the PGRW trajectories.Comment: text shortened, new results added, appearing in J. Phys.

Optimal search strategies for hidden targets

What is the fastest way of finding a randomly hidden target? This question of general relevance is of vital importance for foraging animals. Experimental observations reveal that the search behaviour of foragers is generally intermittent: active search phases randomly alternate with phases of fast ballistic motion. In this letter, we study the efficiency of this type of two states search strategies, by calculating analytically the mean first passage time at the target. We model the perception mecanism involved in the active search phase by a diffusive process. In this framework, we show that the search strategy is optimal when the average duration of "motion phases" varies like the power either 3/5 or 2/3 of the average duration of "search phases", depending on the regime. This scaling accounts for experimental data over a wide range of species, which suggests that the kinetics of search trajectories is a determining factor optimized by foragers and that the perception activity is adequately described by a diffusion process.Comment: 4 pages, 5 figures. to appear in Phys. Rev. Let

Nuclear target search at the single molecule level: protein interactions define the exploration landscape

Gene regulation relies on highly mobile transcription factors (TFs) exploring the nucleoplasm in search of their targets. Our view of the nucleus has evolved from that of an isotropic and homogenous reactor to that of a highly organized yet very dynamic organelle. However important questions remain on how these regulatory factors explore the nuclear environment in search of their DNA or protein targets, and how their exploration strategy affects the kinetics of transcriptional regulation. We implemented a single-molecule tracking assay to determine the TFs dynamics using photoactivatable tags in human cells. We investigated the mobility of several nuclear proteins, including the transcription factor c-Myc and the elongation factor P-TEFb. We found that, while their diffusion speed was comparable, these proteins largely differed in terms of their exploration geometry. We discovered that c-Myc is a global explorer diffusing in the nucleus without spatial constraints. In contrast, the positive transcription elongation factor P-TEFb is a local explorer that oversamples its environment, constrained by a fractal nuclear architecture. Consequently, each c-Myc molecule is equally available for all nuclear sites while P-TEFb reaches its targets in a position-dependent manner. We also measured the mobility of a P-TEFb mutant in which the interaction with the CTD of the RNA Pol II was truncated. In this case, the single-molecule experiments suggested a global exploration of the P-TEFb mutant, consistent with free diffusion. Our observations are in line with a model in which the exploration geometry of TFs is constrained by their interactions and not by exclusion properties. Our findings have strong implications on how proteins react in the nucleus and how their function can be regulated in space and time

Classes of fast and specific search mechanisms for proteins on DNA

Problems of search and recognition appear over different scales in biological systems. In this review we focus on the challenges posed by interactions between proteins, in particular transcription factors, and DNA and possible mechanisms which allow for a fast and selective target location. Initially we argue that DNA-binding proteins can be classified, broadly, into three distinct classes which we illustrate using experimental data. Each class calls for a different search process and we discuss the possible application of different search mechanisms proposed over the years to each class. The main thrust of this review is a new mechanism which is based on barrier discrimination. We introduce the model and analyze in detail its consequences. It is shown that this mechanism applies to all classes of transcription factors and can lead to a fast and specific search. Moreover, it is shown that the mechanism has interesting transient features which allow for stability at the target despite rapid binding and unbinding of the transcription factor from the target.Comment: 65 pages, 23 figure

Intermittent search strategies

This review examines intermittent target search strategies, which combine phases of slow motion, allowing the searcher to detect the target, and phases of fast motion during which targets cannot be detected. We first show that intermittent search strategies are actually widely observed at various scales. At the macroscopic scale, this is for example the case of animals looking for food ; at the microscopic scale, intermittent transport patterns are involved in reaction pathway of DNA binding proteins as well as in intracellular transport. Second, we introduce generic stochastic models, which show that intermittent strategies are efficient strategies, which enable to minimize the search time. This suggests that the intrinsic efficiency of intermittent search strategies could justify their frequent observation in nature. Last, beyond these modeling aspects, we propose that intermittent strategies could be used also in a broader context to design and accelerate search processes.Comment: 72 pages, review articl

Banding, Excitability and Chaos in Active Nematic Suspensions

Motivated by the observation of highly unstable flowing states in suspensions of microtubules and kinesin, we analyze a model of mutually-propelled filaments suspended in a solvent. The system undergoes a mean-field isotropic-nematic transition for large enough filament concentrations when the nematic order parameter is allowed to vary in space and time. We analyze the model in two contexts: a quasi-one-dimensional channel with no-slip walls and a two-dimensional box with periodic boundaries. Using stability analysis and numerical calculations we show that the interplay between non-uniform nematic order, activity, and flow results in a variety of complex scenarios that include spontaneous banded laminar flow, relaxation oscillations, and chaos.Comment: 15 pages, 15 figure

Geometry-controlled kinetics

It has long been appreciated that transport properties can control reaction kinetics. This effect can be characterized by the time it takes a diffusing molecule to reach a target -- the first-passage time (FPT). Although essential to quantify the kinetics of reactions on all time scales, determining the FPT distribution was deemed so far intractable. Here, we calculate analytically this FPT distribution and show that transport processes as various as regular diffusion, anomalous diffusion, diffusion in disordered media and in fractals fall into the same universality classes. Beyond this theoretical aspect, this result changes the views on standard reaction kinetics. More precisely, we argue that geometry can become a key parameter so far ignored in this context, and introduce the concept of "geometry-controlled kinetics". These findings could help understand the crucial role of spatial organization of genes in transcription kinetics, and more generally the impact of geometry on diffusion-limited reactions.Comment: Submitted versio