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Ludger Santen

Publications and source records attributed to Ludger Santen.

At least 37 records · Page 2Linked to original sources

Intracellular transport driven by cytoskeletal motors: General mechanisms and defects

Cells are strongly out-of-equilibrium systems driven by continuous energy supply. They carry out many vital functions requiring active transport of various ingredients and organelles, some being small, others being large. The cytoskeleton, composed of three types of filaments, determines the shape of the cell and plays a role in cell motion. It also serves as a road network for the so-called cytoskeletal motors. These molecules can attach to a cytoskeletal filament, perform directed motion, possibly carrying along some cargo, and then detach. It is a central issue to understand how intracellular transport driven by molecular motors is regulated, in particular because its breakdown is one of the signatures of some neuronal diseases like the Alzheimer. We give a survey of the current knowledge on microtubule based intracellular transport. We first review some biological facts obtained from experiments, and present some modeling attempts based on cellular automata. We start with background knowledge on the original and variants of the TASEP (Totally Asymmetric Simple Exclusion Process), before turning to more application oriented models. After addressing microtubule based transport in general, with a focus on in vitro experiments, and on cooperative effects in the transportation of large cargos by multiple motors, we concentrate on axonal transport, because of its relevance for neuronal diseases. It is a challenge to understand how this transport is organized, given that it takes place in a confined environment and that several types of motors moving in opposite directions are involved. We review several features that could contribute to the efficiency of this transport, including the role of motor-motor interactions and of the dynamics of the underlying microtubule network. Finally, we discuss some still open questions.

physics.bio-ph↗

Length regulation of microtubules by molecular motors: Exact solution and density profiles

In this work we study a microtubule (MT) model, whose length is regulated by the action of processive kinesin motors. We treat the case of infinite processivity, i.e. particle exchange in the bulk is neglected. The exact results can be obtained for model parameters which correspond to a finite length of the MT. In contrast to the model with particle exchange we find that the lengths of the MT are exponentially distributed in this parameter regime. The remaining parameter space of the model, which corresponds to diverging MT lengths, is analyzed by means of extensive Monte Carlo simulations and a macroscopic approach. For divergent MTs we find a complex structure of the phase diagram in terms of shapes of the density profile.

cond-mat.stat-mech↗

Motility states in bidirectional cargo transport

Intracellular cargos which are transported by molecular motors move stochastically along cytoskeleton filaments. In particular for bidirectionally transported cargos it is an open question whether the characteristics of their motion can result from pure stochastic fluctuations or whether some coordination of the motors is needed. The results of a mean-field model of cargo-motors dynamics, which was proposed by Müller et al.[1] suggest the existence of high motility states which would result from a stochastic tug-of-war. Here we analyze a non-mean field extension of their model, that takes explicitly the position of each motor into account. We find that high motility states then disappear. We consider also a mutual motor-motor activation, as an explicit mechanism of motor coordination. We show that the results of the mean-field model are recovered only in case of a strong motor-motor activation in the limit of a high number of motors.

physics.bio-ph↗

Fluctuation effects in bidirectional cargo transport

We discuss a theoretical model for bidirectional cargo transport in biological cells, which is driven by teams of molecular motors and subject to thermal fluctuations. The model describes explicitly the directed motion of the molecular motors on the filament. The motor-cargo coupling is implemented via linear springs. By means of extensive Monte Carlo simulations we show that the model describes the experimentally observed regimes of anomalous diffusion, i.e. subdiffusive behavior at short times followed by superdiffusion at intermediate times. The model results indicate that subdiffuse regime is induced by thermal fluctuations while the superdiffusive motion is generated by correlations of the motors' activity. We also tested the efficiency of bidirectional cargo transport in crowded areas by measuring its ability to pass barriers with increased viscosity. Our results show a remarkable gain of efficiency for high viscosities.

physics.bio-ph↗

Anomalous Diffusion of Self-Propelled Particles in Directed Random Environments

We theoretically study the transport properties of self-propelled particles on complex structures, such as motor proteins on filament networks. A general master equation formalism is developed to investigate the persistent motion of individual random walkers, which enables us to identify the contributions of key parameters: the motor processivity, and the anisotropy and heterogeneity of the underlying network. We prove the existence of different dynamical regimes of anomalous motion, and that the crossover times between these regimes as well as the asymptotic diffusion coefficient can be increased by several orders of magnitude within biologically relevant control parameter ranges. In terms of motion in continuous space, the interplay between stepping strategy and persistency of the walker is established as a source of anomalous diffusion at short and intermediate time scales.

cond-mat.soft↗

Stochastic modeling of cargo transport by teams of molecular motors

Many different types of cellular cargos are transported bidirectionally along microtubules by teams of molecular motors. The motion of this cargo-motors system has been experimentally characterized in vivo as processive with rather persistent directionality. Different theoretical approaches have been suggested in order to explore the origin of this kind of motion. An effective theoretical approach, introduced by Müller et al., describes the cargo dynamics as a tug-of-war between different kinds of motors. An alternative approach has been suggested recently by Kunwar et al., who considered the coupling between motor and cargo in more detail. Based on this framework we introduce a model considering single motor positions which we propagate in continuous time. Furthermore, we analyze the possible influence of the discrete time update schemes used in previous publications on the system's dynamic.

physics.bio-ph↗

Environmental control of microtubule-based bidirectional cargo-transport

Inside cells, various cargos are transported by teams of molecular motors. Intriguingly, the motors involved generally have opposite pulling directions, and the resulting cargo dynamics is a biased stochastic motion. It is an open question how the cell can control this bias. Here we develop a model which takes explicitly into account the elastic coupling of the cargo with each motor. We show that bias can be simply controlled or even reversed in a counterintuitive manner via a change in the external force exerted on the cargo or a variation of the ATP binding rate to motors. Furthermore, the superdiffusive behavior found at short time scales indicates the emergence of motor cooperation induced by cargo-mediated coupling.

physics.bio-ph↗

A bottleneck model for bidirectional transport controlled by fluctuations

We introduce a new model to study the oscillations of opposite flows sharing a common bottleneck and moving on two Totally Asymmetric Simple Exclusion Process (TASEP) lanes. We provide a theoretical analysis of the phase diagram, valid when the flow in the bottleneck is dominated by local stationary states. In particular, we predict and find an inhomogeneous high density phase, with a striped spatio-temporal structure. At the same time, our results also show that some other features of the model cannot be explained by the stationarity hypothesis and require consideration of the transients in the bottleneck at each reversal of the flow. In particular, we show that for short bottlenecks, the capacity of the system is at least as high as for uni-directional flow, in spite of having to empty the bottleneck at each reversal - a feature that can be explained only by efficient transients. Looking at more sensitive quantities like the distribution of flipping times, we show that, in most regimes, the bottleneck is driven by rare fluctuations and descriptions beyond the stationary state are required.

cond-mat.stat-mech↗

Boundary-induced orientation of dynamic filament networks and vesicle agglomerations

We find a statistical mechanism that can adjust orientations of intracellular filaments to cell geometry in absence of organizing centers. The effect is based on random and isotropic filament (de-)polymerization dynamics and is independent of filament interactions and explicit regulation. It can be understood by an analogy to electrostatics and appears to be induced by the confining boundaries; for periodic boundary conditions no orientational bias emerges. Including active transport of particles, the model reproduces experimental observations of vesicle accumulations in transected axons.

physics.bio-ph↗

Asymmetric simple exclusion process in one-dimensional chains with long-range links

We study the boundary-driven asymmetric simple exclusion process (ASEP) in a one-dimensional chain with long-range links. Shortcuts are added to a chain by connecting $pL$ different pairs of sites selected randomly where $L$ and $p$ denote the chain length and the shortcut density, respectively. Particles flow into a chain at one boundary at rate $α$ and out of a chain at the other boundary at rate $β$, while they hop inside a chain via nearest-neighbor bonds and long-range shortcuts. Without shortcuts, the model reduces to the boundary-driven ASEP in a one-dimensional chain which displays the low density, high density, and maximal current phases. Shortcuts lead to a drastic change. Numerical simulation studies suggest that there emerge three phases; an empty phase with $ ρ= 0 $, a jammed phase with $ ρ= 1 $, and a shock phase with $ 0<ρ<1$ where $ρ$ is the mean particle density. The shock phase is characterized with a phase separation between an empty region and a jammed region with a localized shock between them. The mechanism for the shock formation and the non-equilibrium phase transition is explained by an analytic theory based on a mean-field approximation and an annealed approximation.

cond-mat.stat-mech↗

Active transport and cluster formation on 2D networks

We introduce a model for active transport on inhomogeneous networks embedded in a diffusive environment and investigate the formation of particle clusters. In the presence of a hard-core interaction, cluster sizes exhibit an algebraically decaying distribution in a large parameter regime, indicating the existence of clusters on all scales. The results are compared with a diffusion limited aggregation model and active transport on a regular network. For both models we observe aggregation of particles to clusters which are characterized by a finite size-scale if the relevant time-scales and particle densities are considered.

physics.bio-ph↗

Shock-dynamics of two-lane driven lattice gases

Driven lattice gases as the ASEP are useful tools for the modeling of various stochastic transport processes carried out by self-driven particles, such as molecular motors or vehicles in road traffic. Often these processes take place in one-dimensional systems offering several tracks to the particles, and in many cases the particles are able to change track with a given rate. In this work we consider the case of strong coupling where the hopping rate along the tracks and the exchange rates are of the same order, and show how a phenomenological approach based on a domain wall theory can describe the dynamics of the system. In particular, the domain walls on the different tracks form pairs, whose dynamics dominate the behavior of the system.

cond-mat.stat-mech↗

Impact of Short- and Long-range Forces on Protein Conformation and Adsorption Kinetics

We have studied the adsorption kinetics of the protein amylase at solid/liquid interfaces. Offering substrates with tailored properties, we are able to separate the impact of short- and long-range interactions. By means of a colloidal Monte Carlo approach including conformational changes of the adsorbed proteins induced by density fluctuations, we develop a scenario that is consistent with the experimentally observed three-step kinetics on specific substrates. Our observations show that not only the surface chemistry determines the properties of an adsorbed protein layer but also the van der Waals contributions of a composite substrate may lead to non-negligible effects.

cond-mat.soft↗

Partially Asymmetric Exclusion Processes with Sitewise Disorder

We study the stationary properties as well as the non-stationary dynamics of the one-dimensional partially asymmetric exclusion process with position dependent random hop rates. In a finite system of $L$ sites the stationary current, $J$, is determined by the largest barrier and the corresponding waiting time, $τ\sim J^{-1}$, is related to the waiting time of a single random walker, $τ_{rw}$, as $τ\sim τ_{rw}^{1/2}$. The current is found to vanish as: $J \sim L^{-z/2}$, where $z$ is the dynamical exponent of the biased single particle Sinai walk. Typical stationary states are phase separated: At the largest barrier almost all particles queue at one side and almost all holes are at the other side. The high-density (low-density) region, is divided into $\sim L^{1/2}$ connected parts of particles (holes) which are separated by islands of holes (particles) located at the subleading barriers (valleys). We also study non-stationary processes of the system, like coarsening and invasion. Finally we discuss some related models, where particles of larger size or multiple occupation of lattice sites is considered.

cond-mat.stat-mech↗

The partially asymmetric zero range process with quenched disorder

We consider the one-dimensional partially asymmetric zero range process where the hopping rates as well as the easy direction of hopping are random variables. For this type of disorder there is a condensation phenomena in the thermodynamic limit: the particles typically occupy one single site and the fraction of particles outside the condensate is vanishing. We use extreme value statistics and an asymptotically exact strong disorder renormalization group method to explore the properties of the steady state. In a finite system of $L$ sites the current vanishes as $J \sim L^{-z}$, where the dynamical exponent, $z$, is exactly calculated. For $0 1$ the transport is due to the anomalous diffusion of a single Brownian particle. Inactive particles are localized at a second special site and their number in rare realizations is macroscopic. The average density profile of inactive particles has a width of, $ξ\sim δ^{-2}$, in terms of the asymmetry parameter, $δ$. In addition to this, we have investigated the approach to the steady state of the system through a coarsening process and found that the size of the condensate grows as $n_L \sim t^{1/(1+z)}$ for large times. For the unbiased model $z$ is formally infinite and the coarsening is logarithmically slow.

cond-mat.stat-mech↗

An empirical test for cellular automaton models of traffic flow

Based on a detailed microscopic test scenario motivated by recent empirical studies of single-vehicle data, several cellular automaton models for traffic flow are compared. We find three levels of agreement with the empirical data: 1) models that do not reproduce even qualitatively the most important empirical observations, 2) models that are on a macroscopic level in reasonable agreement with the empirics, and 3) models that reproduce the empirical data on a microscopic level as well. Our results are not only relevant for applications, but also shed new light on the relevant interactions in traffic flow.

cond-mat.stat-mech↗

Dynamics of an exclusion process with creation and annihilation

We examine the dynamical properties of an exclusion process with creation and annihilation of particles in the framework of a phenomenological domain-wall theory, by scaling arguments and by numerical simulation. We find that the length- and time scale are finite in the maximum current phase for finite creation- and annihilation rates as opposed to the algebraically decaying correlations of the totally asymmetric simple exclusion process (TASEP). Critical exponents of the transition to the TASEP are determined. The case where bulk creation- and annihilation rates vanish faster than the inverse of the system size N is also analyzed. We point out that shock localization is possible even for rates proportional to 1/N^a, 1<a<2.

cond-mat.stat-mech↗

Relaxation times in the ASEP model using a DMRG method

We compute the largest relaxation times for the totally asymmetric exclusion process (TASEP) with open boundary conditions with a DMRG method. This allows us to reach much larger system sizes than in previous numerical studies. We are then able to show that the phenomenological theory of the domain wall indeed predicts correctly the largest relaxation time for large systems. Besides, we can obtain results even when the domain wall approach breaks down, and show that the KPZ dynamical exponent $z=3/2$ is recovered in the whole maximal current phase.

cond-mat.stat-mech↗