Bidirectional transport and pulsing states in a multi-lane ASEP model

In this paper, we introduce an ASEP-like transport model for bidirectional motion of particles on a multi-lane lattice. The model is motivated by {\em in vivo} experiments on organelle motility along a microtubule (MT), consisting of thirteen protofilaments, where particles are propelled by molecular motors (dynein and kinesin). In the model, organelles (particles) can switch directions of motion due to "tug-of-war" events between counteracting motors. Collisions of particles on the same lane can be cleared by switching to adjacent protofilaments (lane changes). We analyze transport properties of the model with no-flux boundary conditions at one end of a MT ("plus-end" or tip). We show that the ability of lane changes can affect the transport efficiency and the particle-direction change rate obtained from experiments is close to optimal in order to achieve efficient motor and organelle transport in a living cell. In particular, we find a nonlinear scaling of the mean {\em tip size} (the number of particles accumulated at the tip) with injection rate and an associated phase transition leading to {\em pulsing states} characterized by periodic filling and emptying of the system.Comment: 11 figure

Mathematical modelling for bidirectional motor-mediated motility in a fungal model system

In Ustilago maydis hyphae, bidirectional transport of early endosomes (EEs) occurs on microtubules (MTs) that have plus and minus ends. The transport is powered by kinesin-3 towards the plus ends of MTs and dynein towards the minus ends. Experiments show an accumulation of dynein at the MT plus end. To investigate the mechanism of this accumulation, I consider two extended asymmetric simple exclusion principle (ASEP) models for the bidirectional transport of dynein in this thesis. In the simpler two-lane model, collision between opposite-directed motors is excluded whereas the more sophisticated 13-lane model takes into account that the MT usually consists of thirteen protofilaments. The presence of multi protofilaments allows dynein to avoid collision with kinesin by changing protofilaments, a behaviour that has been experimentally described. Both models are supplied by quantitative data obtained in U. maydis by live cell imaging and suggest that the stochastic behaviour of dynein can account for half of dynein motors in the accumulation at the MT plus end. Moreover, for the two-lane model, by using a mean field approximation, I give an analytical approximation for the accumulation size which shows linear dependence on the flux. In contrast, this dependence is nonlinear in the 13-lane model and appears to be associated with a phase transition leading to a "pulsing state". Accompanied experimental studies have shown that U. maydis contains a complex MT array and that kinesin-3 moves early endosomes along antipolar MT bundles. In order to better understand the bidirectional EE motility, I extend the two-lane ASEP to model bidirectional transport along an antipolar MT bundle. In this model, the MTs are coupled at minus ends where organelles can switch MTs on which they move. By a mean-field approximation and numerical simulations, I investigate how the switching affects phases of density profiles as well as the type of motor that dominates the active transport in the bundle

On the mixing properties of piecewise expanding maps under composition with permutations, II: Maps of non-constant orientation

For an integer $m \geq 2$, let $\mathcal{P}_m$ be the partition of the unit interval $I$ into $m$ equal subintervals, and let $\mathcal{F}_m$ be the class of piecewise linear maps on $I$ with constant slope $\pm m$ on each element of $\mathcal{P}_m$. We investigate the effect on mixing properties when $f \in \mathcal{F}_m$ is composed with the interval exchange map given by a permutation $\sigma \in S_N$ interchanging the $N$ subintervals of $\mathcal{P}_N$. This extends the work in a previous paper [N.P. Byott, M. Holland and Y. Zhang, DCDS, {\bf 33}, (2013) 3365--3390], where we considered only the "stretch-and-fold" map $f_{sf}(x)=mx \bmod 1$.Comment: 27 pages 6 figure

Modeling the geometry of the endoplasmic reticulum network

Conference ProceedingFirst International Conference, AlCoB 2014, held in July 2014 in Tarragona, Spain.We have studied the network geometry of the endoplasmic reticulum by means of graph theoretical and integer programming models. The purpose is to represent this structure as close as possible by a class of finite, undirected and connected graphs the nodes of which have to be either of degree three or at most of degree three. We determine plane graphs of minimal total edge length satisfying degree and angle constraints, and we show that the optimal graphs are close to the ER network geometry. Basically, two procedures are formulated to solve the optimization problem: a binary linear program, that iteratively constructs an optimal solution, and a linear program, that iteratively exploits additional cutting planes from different families to accelerate the solution process. All formulations have been implemented and tested on a series of real-life and randomly generated cases. The cutting plane approach turns out to be particularly efficient for the real-life testcases, since it outperforms the pure integer programming approach by a factor of at least 10. © 2014 Springer International Publishing

Motor-mediated bidirectional transport along an antipolar microtubule bundle: A mathematical model

Copyright © 2013 American Physical SocietyLong-distance bidirectional transport of organelles depends on the coordinated motion of various motor proteins on the cytoskeleton. Recent quantitative live cell imaging in the elongated hyphal cells of Ustilago maydis has demonstrated that long-range motility of motors and their endosomal cargo occurs on unipolar microtubules (MTs) near the extremities of the cell. These MTs are bundled into antipolar bundles within the central part of the cell. Dynein and kinesin-3 motors coordinate their activity to move early endosomes (EEs) in a bidirectional fashion where dynein drives motility towards MT minus ends and kinesin towards MT plus ends. Although this means that one can easily assign the drivers of bidirectional motion in the unipolar section, the bipolar orientations in the bundle mean that it is possible for either motor to drive motion in either direction. In this paper we use a multilane asymmetric simple exclusion process modeling approach to simulate and investigate phases of bidirectional motility in a minimal model of an antipolar MT bundle. In our model, EE cargos (particles) change direction on each MT with a turning rate Ω and there is switching between MTs in the bundle at the minus ends. At these ends, particles can hop between MTs with rate q1 on passing from a unipolar to a bipolar section (the obstacle-induced switching rate) or q2 on passing in the other direction (the end-induced switching rate). By a combination of numerical simulations and mean-field approximations, we investigate the distribution of particles along the MTs for different values of these parameters and of Θ, the overall density of particles within this closed system. We find that even if Θ is low, the system can exhibit a variety of phases with shocks in the density profiles near plus and minus ends caused by queuing of particles. We discuss how the parameters influence the type of particle that dominates active transport in the bundle

Queueing induced by bidirectional motor motion near the end of a microtubule

© 2010 The American Physical SocietyRecent live observations of motors in long-range microtubule (MT) dependent transport in the fungus Ustilago maydis have reported bidirectional motion of dynein and an accumulation of the motors at the polymerization-active (the plus-end) of the microtubule. Quantitative data derived from in vivo observation of dynein has enabled us to develop an accurate, quantitatively-valid asymmetric simple exclusion process (ASEP) model that describes the coordinated motion of anterograde and retrograde motors sharing a single oriented microtubule. We give approximate expressions for the size and distribution of the accumulation, and discuss queueing properties for motors entering this accumulation. We show for this ASEP model, that the mean accumulation can be modeled as an M/M/∞ queue that is Poisson distributed with mean F(arr)/p(d), where F(arr) is the flux of motors that arrives at the tip and p(d) is the rate at which individual motors change direction from anterograde to retrograde motion. Deviations from this can in principle be used to gain information about other processes at work in the accumulation. Furthermore, our work is a significant step toward a mathematical description of the complex interactions of motors in cellular long-range transport of organelles