Insights into cytoskeletal behavior from computational modeling of dynamic microtubules in a cell-like environment

Gregoretti, Ivan V.; Margolin, Gennady; Alber, Mark; Goodson, Holly V.

doi:10.1242/jcs.03240

Cited by 53 publications

(87 citation statements)

References 43 publications

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“…Similar results were obtained with models describing explicitely the GTP cap [144]. Note that we only consider the case of a sufficiently high concentration of tubulin, so that the growth of MTs is not limited before the cell edge is reached [144].…”

Section: Dynamic Mts In Finite Volumesupporting

confidence: 75%

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Intracellular transport driven by cytoskeletal motors: General mechanisms and defects

2015

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Cells are the elementary units of living organisms, which are able to carry out many vital functions. These functions rely on active processes on a microscopic scale. Therefore, they are strongly out-of-equilibrium systems, which are driven by continuous energy supply. The tasks that have to be performed in order to maintain the cell alive require transportation of various ingredients, some being small, others being large. Intracellular transport processes are able to induce concentration gradients and to carry objects to specific targets. These processes cannot be carried out only by diffusion, as cells may be crowded, and quite elongated on molecular scales. Therefore active transport has to be organized.The cytoskeleton, which is composed of three types of filaments (microtubules, actin and intermediate filaments), determines the shape of the cell, and plays a role in cell motion. It also serves as a road network for a special kind of vehicles, namely the 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. The interest for this type of question was enhanced when it was discovered that intracellular transport 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. Our review includes on the one hand an overview of biological facts, obtained from experiments, and on the other hand a presentation of some modeling attempts based on cellular automata. We present some 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. Some important characteristics of axonal transport is that it takes place in a confined environment; Besides several types of motors are involved, that move in opposite directions. It is a challenge to understand how this bidirectional transport is organized. We review several features that could contribute to the efficiency of bidirectional transport in the axon, including in particular the role of motor-motor interactions and of the dynamics of the underlying microtubule network. Finally, we also discuss some open questions that may be relevant for future research in this field.

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Section: Dynamic Mts In Finite Volumesupporting

confidence: 75%

“…Note that we only consider the case of a sufficiently high concentration of tubulin, so that the growth of MTs is not limited before the cell edge is reached [144].…”

Section: Dynamic Mts In Finite Volumementioning

confidence: 99%

Intracellular transport driven by cytoskeletal motors: General mechanisms and defects

2015

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“…The coexistence of minus-end depolymerization and plus-end polymerization of a single MT is responsible for its treadmilling observed in experiments (9,12). In simulation, a maximum MT length L m (with reflective boundary condition) is assigned to approximate the complicated regulation and confinement of MT length in cells (18,25,29) (see SI Text and Fig. S10).…”

Section: Methodsmentioning

confidence: 99%

Understanding phase behavior of plant cell cortex microtubule organization

Shi

2010

Proc. Natl. Acad. Sci. U.S.A.

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Plant microtubules are found to be strongly associated with the cell cortex and to experience polymerization/depolymerization processes that are responsible for the organization of microtubule cortical array. Here we propose a minimal model that incorporates the basic assembly dynamics and intermicrotubule interaction to understand the unexplored phase behavior of such a system. Through kinetic Monte Carlo simulations and theoretical calculations, we show that the self-organized patterns of plant cell cortical microtubules can be regulated by controlling single microtubule assembly dynamics. Biologically, this means that the structural reorganization can be regulated by microtubule-associated proteins via changing microtubule dynamic instability parameters, such as the microtubule plus-end growing rate, GTP-tubulin hydrolysis rate, etc. Such regulation is indirectly confirmed by various in vivo experiments. For the physical aspects, we not only construct the phase diagram that determines under what parameters ordered microtubule arrays form, but also predict that the essentially different ordered structures may appear through continuous and discontinuous transitions. The present study will play a central role in our understanding of the basic mechanism of plant cell noncentrosomal microtubule arrays.cortical microtubule array | cytoskeleton | nematic phase | treadmilling | steric interaction U nderstanding the structural organization of the microtubule (MT) cytoskeleton is a central problem in cell biology (1-4). In plant cell, MTs are confined to a thin layer of the interior side of the plasma membrane and may organize into the so-called cortical MT array-a highly ordered structure just beneath the plasma membrane. In contrast to equilibrium ordered structures, such a MT cortical array, which is unique in the plant cell, constantly changes its appearance and even may disappear and reform during different phases of cell cycle (5-7). One open question is how the plant cell regulates the formation of cortical arrays and what dictates the self-organized patterns of MTs. From a physical point of view, it is also interesting to understand these phenomena by asking how the ordered structures are achieved through the noncentrosomal MT cortical organization and whether there are any basic mechanisms governing such dynamic order transitions.Recent in vivo experimental studies have made great progress in revealing the possible formation of plant cell cortical arrays (5,8). Unlike animal cells, the nucleation of new MTs is found to be widely dispersed on plasma membrane (9-11), because of the lack of centrioles in plant cells. MTs are found stably attached to the membrane, and therefore lateral and rotational diffusions of MTs are suppressed. Instead, treadmilling behavior of MTs, which is achieved by plus-end polymerization and minusend depolymerization, was observed on the plasma membrane (9, 10), and consequent intermicrotubule collisions may frequently occur between a polymerizing MT and a preexisting one (9, 12). If t...

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“…This effect may partially account for the observation that MTs in cells frequently undergo catastrophe when they reach the cell edge [49]. This "premature" induction of catastrophe by the cell edge may in turn increase the amount of unpolymerized tubulin and contribute to the observed persistent growth of MTs in the cell interior [50]. These examples of how physical considerations contribute in a fundamental way to cytoskeletal behavior in vitro are but a few of those that will facilitate our understanding of in vivo dynamics in the future.…”

Section: Implications For In Vivo Regulation Of Mt Dynamicsmentioning

confidence: 99%

Microtubule assembly dynamics: new insights at the nanoscale

Gardner

Hunt

Goodson

et al. 2008

Current Opinion in Cell Biology

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Although the dynamic self-assembly behavior of microtubule ends has been well characterized at the spatial resolution of light microscopy (∼200 nm), the single-molecule events that lead to these dynamics are less clear. Recently, a number of in vitro studies used novel approaches combining laser tweezers, microfabricated chambers, and high-resolution tracking of microtubule-bound beads to characterize mechanochemical aspects of MT dynamics at nanometer scale resolution. In addition, computational modeling is providing a framework for integrating these experimental results into physically plausible models of molecular scale microtubule dynamics. These nanoscale studies are providing new fundamental insights about microtubule assembly, and will be important for advancing our understanding of how microtubule dynamic instability is regulated in vivo via microtubuleassociated proteins, therapeutic agents, and mechanical forces.

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Insights into cytoskeletal behavior from computational modeling of dynamic microtubules in a cell-like environment

Abstract: SummaryInsights into cytoskeletal behavior from computational modeling of dynamic microtubules in a cell-like environment

Cited by 53 publications

References 43 publications

Intracellular transport driven by cytoskeletal motors: General mechanisms and defects

Intracellular transport driven by cytoskeletal motors: General mechanisms and defects

Understanding phase behavior of plant cell cortex microtubule organization

Microtubule assembly dynamics: new insights at the nanoscale

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