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.Comment: 74 pages, 43 figure

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 M\"uller 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.Comment: 6 pages, 10 figure

Macroscopic relaxation after on-ramps in real data and in cellular automata simulations

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Experimental Study of Collective Pedestrian Dynamics

International audienceWe report on two series of experiments, conducted in the frame of two different collaborations designed to study how pedestrians adapt their trajectories and velocities in groups or crowds. Strong emphasis is put on the motivations for the chosen protocols and the experimental implementation. The first series deals with pattern formation, interactions between pedestrians, and decision-making in pedestrian groups at low to medium densities. In particular, we show how pedestrians adapt their headways in single-file motion depending on the (prescribed) leader's velocity. The second series of experiments focuses on static crowds at higher densities, a situation that can be critical in real life and in which the pedestrians' choices of motion are strongly constrained sterically. More precisely, we study the crowd's response to its crossing by a pedestrian or a cylindrical obstacle of 74cm in diameter. In the latter case, for a moderately dense crowd, we observe displacements that quickly decay with the minimal distance to the obstacle, over a lengthscale of the order of the meter

Modeling crowd dynamics through coarse-grained data analysis

International audienceUnderstanding and predicting the collective behaviour of crowds is essential to improve the efficiency of pedestrian flows in urban areas and minimize the risks of accidents at mass events. We advocate for the development of crowd traffic management systems, whereby observations of crowds can be coupled to fast and reliable models to produce rapid predictions of the crowd movement and eventually help crowd managers choose between tailored optimization strategies. Here, we propose a Bi-directional Macroscopic (BM) model as the core of such a system. Its key input is the fundamental diagram for bi-directional flows, i.e. the relation between the pedestrian fluxes and densities. We design and run a laboratory experiments involving a total of 119 participants walking in opposite directions in a circular corridor and show that the model is able to accurately capture the experimental data in a typical crowd forecasting situation. Finally, we propose a simple segregation strategy for enhancing the traffic efficiency, and use the BM model to determine the conditions under which this strategy would be beneficial. The BM model, therefore, could serve as a building block to develop on the fly prediction of crowd movements and help deploying real-time crowd optimization strategies