Brain-wide dendrites in a near-optimal performance of dynamic range and information transmission.

Dendrites receive and process signals from other neurons. The range of signal intensities that can be robustly distinguished by dendrites is quantified by the dynamic range. We investigate the dynamic range and information transmission efficiency of dendrites in relation to dendritic morphology. We model dendrites in a neuron as multiple excitable binary trees connected to the soma where each node in a tree can be excited by external stimulus or by receiving signals transmitted from adjacent excited nodes. It has been known that larger dendritic trees have a higher dynamic range. We show that for dendritic tress of the same number of nodes, the dynamic range increases with the number of somatic branches and decreases with the asymmetry of dendrites, and the information transmission is more efficient for dendrites with more somatic branches. Moreover, our simulated data suggest that there is an exponential association (decay resp.) of overall relative energy consumption (dynamic range resp.) in relation to the number of somatic branches. This indicates that further increasing the number of somatic branches (e.g. beyond 10 somatic branches) has limited ability to improve the transmission efficiency. With brain-wide neuron digital reconstructions of the pyramidal cells, 90% of neurons have no more than 10 dendrites. These suggest that actual brain-wide dendritic morphology is near optimal in terms of both dynamic range and information transmission.

Asynchronous changes of normal lung lobes during respiration based on quantitative computed tomography (CT).

Background: This study aimed to explore the coordinated and independent actions of lung lobes during respiration using quantitative computed tomography (CT) in order to increase our in vivo understanding of pulmonary anatomy. Methods: Cases for whom test results showed normal pulmonary function tests (PFTs) results, and normal paired inspiratory-expiratory chest CT findings, as assessed by 2 radiologists, were retrospectively included in this study. From the chest CT results, we measured quantitative indices of lung volume (LV) and mean lung density (MLD) for the total lung (TL), left lung (LL), right lung (RL), and 5 lobes in inspiratory and expiratory phases. The differences of these measures between bilateral lungs and among the lobes were evaluated to study whether they were consistent or different during respiration. Results: A total of 70 cases were included {median age of 49.5 [interquartile range (IQR), 38.0 to 60.3] years; 32 males; 38 females}. Overall, the inspiratory and expiratory volumes of the LL were smaller than those of the RL (both P<0.001). For the ventilation workload (λ, which indicates the ratio of lobar volume to total LV), the end-expiratory volume ratio (λex ) of the LL was 0.44 (IQR, 0.43 to 0.46), while the end-inspiratory volume ratio (λin ) had risen to 0.46 (IQR, 0.45 to 0.47) (P<0.001). Comparing the 5 lobes, not all lobes shared the same LV. However, the left lower lobe (LLL) and right lower lobe (RLL) showed some similarities. The λin-LLL and λin-RLL was higher than λex-LLL and λex-RLL , respectively (both P<0.001), while the ratios of the other lobes reduced. The pairwise mean absolute difference (PMAD) on λin and λex of the bilateral lower lobes was low in inspiration (0.0288) and expiration (0.0346). The MLD of bilateral lower lobes showed consistency in inspiration or in expiration (inspiration: P>0.999; expiration: P=0.975). In addition, the PMADs between the right middle lobe (RML) and other lobes were significantly larger than the PMAD between other pairs of lobes in both inspiration and expiration. Beyond that, the expiratory MLD of RML [-789.6 (IQR, -814 to -762.05) HU] was the lowest among the 5 lobes. Conclusions: We found that the LL assumes a higher workload during ventilation than it does during respiration. The 5 normal lobes were non-synchronous during respiration and contributed differently to ventilation. The bilateral lower lobes showed similarities and had a high-ventilation function, while and the LV and MLD of the RML showed the least changes within a respiration cycle.

Miro2 tethers the ER to mitochondria to promote mitochondrial fusion in tobacco leaf epidermal cells.

Mitochondria are highly pleomorphic, undergoing rounds of fission and fusion. Mitochondria are essential for energy conversion, with fusion favouring higher energy demand. Unlike fission, the molecular components involved in mitochondrial fusion in plants are unknown. Here, we show a role for the GTPase Miro2 in mitochondria interaction with the ER and its impacts on mitochondria fusion and motility. Mutations in AtMiro2's GTPase domain indicate that the active variant results in larger, fewer mitochondria which are attached more readily to the ER when compared with the inactive variant. These results are contrary to those in metazoans where Miro predominantly controls mitochondrial motility, with additional GTPases affecting fusion. Synthetically controlling mitochondrial fusion rates could fundamentally change plant physiology by altering the energy status of the cell. Furthermore, altering tethering to the ER could have profound effects on subcellular communication through altering the exchange required for pathogen defence.

Modeling the Geometry and Dynamics of the Endoplasmic Reticulum Network.

The endoplasmic reticulum (ER) is an intricate network that pervades the entire cortex of plant cells and its geometric shape undergoes drastic changes. This paper proposes a mathematical model to reconstruct geometric network dynamics by combining the node movements within the network and topological changes engendered by these nodes. The network topology in the model is determined by a modified optimization procedure from the work (Lemarchand, et al. 2014) which minimizes the total length taking into account both degree and angle constraints, beyond the conditions of connectedness and planarity. A novel feature for solving our optimization problem is the use of "lifted" angle constraints, which allows one to considerably reduce the solution runtimes. Using this optimization technique and a Langevin approach for the branching node movement, the simulated network dynamics represent the ER network dynamics observed under latrunculin B treated condition and recaptures features such as the appearance/disappearance of loops within the ER under the native condition. The proposed modeling approach allows quantitative comparison of networks between the model and experimental data based on topological changes induced by node dynamics. An increased temporal resolution of experimental data will allow a more detailed comparison of network dynamics using this modeling approach.

Modeling Endoplasmic Reticulum Network Maintenance in a Plant Cell.

The endoplasmic reticulum (ER) in plant cells forms a highly dynamic network of complex geometry. ER network morphology and dynamics are influenced by a number of biophysical processes, including filament/tubule tension, viscous forces, Brownian diffusion, and interactions with many other organelles and cytoskeletal elements. Previous studies have indicated that ER networks can be thought of as constrained minimal-length networks acted on by a variety of forces that perturb and/or remodel the network. Here, we study two specific biophysical processes involved in remodeling. One is the dynamic relaxation process involving a combination of tubule tension and viscous forces. The other is the rapid creation of cross-connection tubules by direct or indirect interactions with cytoskeletal elements. These processes are able to remodel the ER network: the first reduces network length and complexity whereas the second increases both. Using live cell imaging of ER network dynamics in tobacco leaf epidermal cells, we examine these processes on ER network dynamics. Away from regions of cytoplasmic streaming, we suggest that the dynamic network structure is a balance between the two processes, and we build an integrative model of the two processes for network remodeling. This model produces quantitatively similar ER networks to those observed in experiments. We use the model to explore the effect of parameter variation on statistical properties of the ER network.

Active diffusion and microtubule-based transport oppose myosin forces to position organelles in cells.

Even distribution of peroxisomes (POs) and lipid droplets (LDs) is critical to their role in lipid and reactive oxygen species homeostasis. How even distribution is achieved remains elusive, but diffusive motion and directed motility may play a role. Here we show that in the fungus Ustilago maydis ∼95% of POs and LDs undergo diffusive motions. These movements require ATP and involve bidirectional early endosome motility, indicating that microtubule-associated membrane trafficking enhances diffusion of organelles. When early endosome transport is abolished, POs and LDs drift slowly towards the growing cell end. This pole-ward drift is facilitated by anterograde delivery of secretory cargo to the cell tip by myosin-5. Modelling reveals that microtubule-based directed transport and active diffusion support distribution, mobility and mixing of POs. In mammalian COS-7 cells, microtubules and F-actin also counteract each other to distribute POs. This highlights the importance of opposing cytoskeletal forces in organelle positioning in eukaryotes.

Structure and dynamics of ER: minimal networks and biophysical constraints.

The endoplasmic reticulum (ER) in live cells is a highly mobile network whose structure dynamically changes on a number of timescales. The role of such drastic changes in any system is unclear, although there are correlations with ER function. A better understanding of the fundamental biophysical constraints on the system will allow biologists to determine the effects of molecular factors on ER dynamics. Previous studies have identified potential static elements that the ER may remodel around. Here, we use these structural elements to assess biophysical principles behind the network dynamics. By analyzing imaging data of tobacco leaf epidermal cells under two different conditions, i.e., native state (control) and latrunculin B (treated), we show that the geometric structure and dynamics of ER networks can be understood in terms of minimal networks. Our results show that the ER network is well modeled as a locally minimal-length network between the static elements that potentially anchor the ER to the cell cortex over longer timescales; this network is perturbed by a mixture of random and deterministic forces. The network need not have globally minimum length; we observe cases where the local topology may change dynamically between different Euclidean Steiner network topologies. The networks in the treated cells are easier to quantify, because they are less dynamic (the treatment suppresses actin dynamics), but the same general features are found in control cells. Using a Langevin approach, we model the dynamics of the nonpersistent nodes and use this to show that the images can be used to estimate both local viscoelastic behavior of the cytoplasm and filament tension in the ER network. This means we can explain several aspects of the ER geometry in terms of biophysical principles.

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

Long-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 q(1) on passing from a unipolar to a bipolar section (the obstacle-induced switching rate) or q(2) 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.

Controlled and stochastic retention concentrates dynein at microtubule ends to keep endosomes on track.

Bidirectional transport of early endosomes (EEs) involves microtubules (MTs) and associated motors. In fungi, the dynein/dynactin motor complex concentrates in a comet-like accumulation at MT plus-ends to receive kinesin-3-delivered EEs for retrograde transport. Here, we analyse the loading of endosomes onto dynein by combining live imaging of photoactivated endosomes and fluorescent dynein with mathematical modelling. Using nuclear pores as an internal calibration standard, we show that the dynein comet consists of ∼55 dynein motors. About half of the motors are slowly turned over (T(1/2): ∼98 s) and they are kept at the plus-ends by an active retention mechanism involving an interaction between dynactin and EB1. The other half is more dynamic (T(1/2): ∼10 s) and mathematical modelling suggests that they concentrate at MT ends because of stochastic motor behaviour. When the active retention is impaired by inhibitory peptides, dynein numbers in the comet are reduced to half and ∼10% of the EEs fall off the MT plus-ends. Thus, a combination of stochastic accumulation and active retention forms the dynein comet to ensure capturing of arriving organelles by retrograde motors.