Directed Transport
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2022 ◽  
pp. 117107
Author(s):  
Junping Gu ◽  
Guang Zhang ◽  
Qinggong Wang ◽  
Chao Wang ◽  
Yiwei Liu ◽  
...  

Author(s):  
Li Li ◽  
Fang Fang ◽  
Jiajia Li ◽  
Guobing Zhou ◽  
Zhen Yang

An in-depth understanding of directed transport behaviors of water molecules through nanoporous materials is essential for the design and development of next-generation filtration devices. In this work, we perform molecular...


Author(s):  
S. Walcott ◽  
D. M. Warshaw

Myosin Va (myoVa) motors transport membrane-bound cargo through three-dimensional, intracellular actin filament networks. We developed a coarse-grained, in silico model to predict how actin filament density (3-800 filaments) within a randomly oriented actin network affects fluid-like liposome (350nm vs. 1,750nm) transport by myoVa motors. 5,000 simulated liposomes transported within each network adopted one of three states: transport, tug of war, or diffusion. Diffusion due to liposome detachment from actin rarely occurred given at least 10 motors on the liposome surface. However, with increased actin density, liposomes transitioned from primarily directed transport on single actin filaments to an apparent random walk, resulting from a mixture of transport and tug of wars as the probability of encountering additional actin filaments increased. This phase transition arises from a percolation phase transition at a critical number of accessible actin filaments, Nc. Nc is a geometric property of the actin network that depends only on the position and polarity of the actin filaments, transport distance, and the liposome diameter, as evidenced by a five-fold increase in liposome diameter resulting in a five-fold decrease in Nc. Thus, in cells, actin network density and cargo size may be regulated to match cargo delivery to the cell's physiological demands. [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text]


2021 ◽  
Vol 9 (11) ◽  
pp. 1300
Author(s):  
Troels Aagaard ◽  
Joost Brinkkemper ◽  
Drude F. Christensen ◽  
Michael G. Hughes ◽  
Gerben Ruessink

The existence of sandy beaches relies on the onshore transport of sand by waves during post-storm conditions. Most operational sediment transport models employ wave-averaged terms, and/or the instantaneous cross-shore velocity signal, but the models often fail in predictions of the onshore-directed transport rates. An important reason is that they rarely consider the phase relationships between wave orbital velocity and the suspended sediment concentration. This relationship depends on the intra-wave structure of the bed shear stress and hence on the timing and magnitude of turbulence production in the water column. This paper provides an up-to-date review of recent experimental advances on intra-wave turbulence characteristics, sediment mobilization, and suspended sediment transport in laboratory and natural surf zones. Experimental results generally show that peaks in the suspended sediment concentration are shifted forward on the wave phase with increasing turbulence levels and instantaneous near-bed sediment concentration scales with instantaneous turbulent kinetic energy. The magnitude and intra-wave phase of turbulence production and sediment concentration are shown to depend on wave (breaker) type, seabed configuration, and relative wave height, which opens up the possibility of more robust predictions of transport rates for different wave and beach conditions.


Author(s):  
Erin M. Masucci ◽  
Peter K. Relich ◽  
Melike Lakadamyali ◽  
E. Michael Ostap ◽  
Erika L. F. Holzbaur

Microtubules establish the directionality of intracellular transport by kinesins and dynein through polarized assembly, but it remains unclear how directed transport occurs along microtubules organized with mixed polarity. We investigated the ability of the plus-end directed kinesin-4 motor KIF21B to navigate mixed polarity microtubules in mammalian dendrites. Reconstitution assays with recombinant KIF21B and engineered microtubule bundles or extracted neuronal cytoskeletons indicate that nucleotide-independent microtubule binding regions of KIF21B modulate microtubule dynamics and promote directional switching on antiparallel microtubules. Optogenetic recruitment of KIF21B to organelles in live neurons induces unidirectional transport in axons but bi-directional transport with a net retrograde bias in dendrites. Removal of the secondary microtubule binding regions of KIF21B or dampening of microtubule dynamics with low concentrations of nocodazole eliminates retrograde bias in live dendrites. Further exploration of the contribution of microtubule dynamics in dendrites to directionality revealed plus-end-out microtubules to be more dynamic than plus-end-in microtubules, with nocodazole preferentially stabilizing the plus-end-out population. We propose a model in which both nucleotide-sensitive and insensitive microtubule binding sites of KIF21B motors contribute to the search and selection of stable plus-end-in microtubules within the mixed polarity microtubule arrays characteristic of mammalian dendrites to achieve net retrograde movement of KIF21B-bound cargos. [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text]


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Lance T. Denes ◽  
Chase P. Kelley ◽  
Eric T. Wang

AbstractWhile the importance of RNA localization in highly differentiated cells is well appreciated, basic principles of RNA localization in skeletal muscle remain poorly characterized. Here, we develop a method to detect and quantify single molecule RNA localization patterns in skeletal myofibers, and uncover a critical role for directed transport of RNPs in muscle. We find that RNAs localize and are translated along sarcomere Z-disks, dispersing tens of microns from progenitor nuclei, regardless of encoded protein function. We find that directed transport along the lattice-like microtubule network of myofibers becomes essential to achieve this localization pattern as muscle development progresses; disruption of this network leads to extreme accumulation of RNPs and nascent protein around myonuclei. Our observations suggest that global active RNP transport may be required to distribute RNAs in highly differentiated cells and reveal fundamental mechanisms of gene regulation, with consequences for myopathies caused by perturbations to RNPs or microtubules.


2021 ◽  
Vol 10 (3) ◽  
pp. 38-46
Author(s):  
D. A. Petrukhina ◽  
I. V. Pletneva ◽  
B. B. Sysuev

Introduction. Liver diseases with all the variety of clinical manifestations have common pathogenetic links at the cellular level. The group of hepatoprotective agents is represented by drugs that exhibit versatile mechanisms for protecting liver cells from the effects of damaging factors, the main of which are membrane-stabilizing, antioxidant, regenerative, detoxifying, choleretic and anti-inflammatory effects. The high therapeutic and hepatoprotective effectiveness of modern drugs is largely due to their metabolic effects, as well as their ability to bind free radicals and reactive oxygen species in the cell.Text. The purpose of this work is to form an analytical review of the literature on the assortment and concepts of improving the dosage forms of hepatoprotective agents. According to the analysis and systematization of modern publications devoted to the use of hepatoprotectors in the treatment of liver diseases, it is shown that it is necessary to develop new formulations and combinations of biologically active substances with the manifestation of versatile mechanisms of hepatoprotection, as well as to improve the composition and manufacturing technologies of existing traditional therapies. One of the current trends is the use of new substances in the development of traditional and innovative dosage forms. The search for biologically active molecules with antioxidant, antiradical and membrane-stabilizing activity that can be considered as effective hepatoprotectors continues. An integral task of pharmaceutical development is the creation of bioavailable drugs that have a prolonged effect and minimal side effects. A promising direction in pharmaceutical technology is the development of innovative drugs for the directed transport of biologically active molecules to the affected organ.Conclusion. As a result of the analysis of modern data, priority directions for the development and improvement of existing formulations based on modern approaches to the production of innovative dosage forms are identified. The relevance of improving the dosage forms of hepatoprotectors presented on the pharmaceutical market is shown. Of particular interest is the development of innovative targeted delivery systems with effective and safe hepatoprotectors in various combinations, including those based on cinnamic acid derivatives.


2021 ◽  
Author(s):  
Sam Walcott ◽  
David M Warshaw

Myosin Va (myoVa) motors transport membrane-bound cargo through three-dimensional, intracellular actin filament networks. We developed a coarse-grained, in silico model to predict how actin filament density (3-800 filaments) within a randomly oriented actin network affects fluid-like liposome (350nm vs. 1,750nm) transport by myoVa motors. 5,000 simulated liposomes transported within each network adopted one of three states: transport, tug of war, or diffusion. Diffusion due to liposome detachment from actin rarely occurred given at least 10 motors on the liposome surface. However, with increased actin density, liposomes transitioned from primarily directed transport on single actin filaments to an apparent random walk, resulting from a mixture of transport and tug of wars as the probability of encountering additional actin filaments increased. This phase transition arises from a percolation phase transition at a critical number of accessible actin filaments, Nc. Nc, is a geometric property of the actin network that depends only on the position and polarity of the actin filaments and the liposome diameter, as evidenced by a five-fold increase in liposome diameter resulting in a five-fold decrease in Nc. Thus, in cells, actin network density and cargo size may be regulated to match cargo delivery to the cell's physiological demands.


2021 ◽  
Vol 17 (7) ◽  
pp. e1009258
Author(s):  
Justin Torok ◽  
Pedro D. Maia ◽  
Parul Verma ◽  
Christopher Mezias ◽  
Ashish Raj

Defects in axonal transport may partly underpin the differences between the observed pathophysiology of Alzheimer’s disease (AD) and that of other non-amyloidogenic tauopathies. Particularly, pathological tau variants may have molecular properties that dysregulate motor proteins responsible for the anterograde-directed transport of tau in a disease-specific fashion. Here we develop the first computational model of tau-modified axonal transport that produces directional biases in the spread of tau pathology. We simulated the spatiotemporal profiles of soluble and insoluble tau species in a multicompartment, two-neuron system using biologically plausible parameters and time scales. Changes in the balance of tau transport feedback parameters can elicit anterograde and retrograde biases in the distributions of soluble and insoluble tau between compartments in the system. Aggregation and fragmentation parameters can also perturb this balance, suggesting a complex interplay between these distinct molecular processes. Critically, we show that the model faithfully recreates the characteristic network spread biases in both AD-like and non-AD-like mouse tauopathy models. Tau transport feedback may therefore help link microscopic differences in tau conformational states and the resulting variety in clinical presentations.


2021 ◽  
Author(s):  
Elaine B Schenk ◽  
Frederic A Meunier ◽  
Dietmar B Oelz

Through the integration of results from an imaging analysis of intracellular trafficking of labelled neurosecretory vesicles in chromaffin cells, we develop a Markov state model to describe their transport and binding kinetics. Our simulation results indicate that a spatial redistribution of neurosecretory vesicles occurs upon secretagogue stimulation leading vesicles to the plasma membrane where they undergo fusion thereby releasing adrenaline and noradrenaline. Furthermore, we find that this redistribution alone can explain the observed up-regulation of vesicle transport upon stimulation and its directional bias towards the plasma membrane. Parameter fitting indicates that in the deeper compartment within the cell, vesicle transport is asymmetric and characterised by a bias towards the plasma membrane. We also find that crowding of neurosecretory vesicles undergoing directed transport explains the observed accelerated recruitment of freely diffusing vesicles into directed transport upon stimulation.


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