Effects of spatial dimensionality and steric interactions on microtubule-motor self-organization

Rickman, Jamie; Nédélec, François; Surrey, Thomas

doi:10.1088/1478-3975/ab0fb1

Cited by 18 publications

(21 citation statements)

References 50 publications

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“…In contrast to MEDYAN, other cytoskeletal modeling strategies, such as Cytosim (Cytoskeletal Simulation) [66,67], AFINES (Active Filament Network Simulation) [68], and the model by Kim and coworkers [41] rely on the Langevin dynamics of cytoskeletal components, explicitly simulating thermal undulations at the expense of significant diminution of computational efficiency. Among these models, MEDYAN’s treatment of general reaction-diffusion processes is most comprehensive (in particular, with regard to G-actin’s diffusion and reactions).…”

Section: Methodsmentioning

confidence: 99%

Remarkable structural transformations of actin bundles are driven by their initial polarity, motor activity, crosslinking, and filament treadmilling

2019

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Bundled actin structures play a key role in maintaining cellular shape, in aiding force transmission to and from extracellular substrates, and in affecting cellular motility. Recent studies have also brought to light new details on stress generation, force transmission and contractility of actin bundles. In this work, we are primarily interested in the question of what determines the stability of actin bundles and what network geometries do unstable bundles eventually transition to. To address this problem, we used the MEDYAN mechano-chemical force field, modeling several micron-long actin bundles in 3D, while accounting for a comprehensive set of chemical, mechanical and transport processes. We developed a hierarchical clustering algorithm for classification of the different long time scale morphologies in our study. Our main finding is that initially unipolar bundles are significantly more stable compared with an apolar initial configuration. Filaments within the latter bundles slide easily with respect to each other due to myosin activity, producing a loose network that can be subsequently severely distorted. At high myosin concentrations, a morphological transition to aster-like geometries was observed. We also investigated how actin treadmilling rates influence bundle dynamics, and found that enhanced treadmilling leads to network fragmentation and disintegration, while this process is opposed by myosin and crosslinking activities. Interestingly, treadmilling bundles with an initial apolar geometry eventually evolve to a whole gamut of network morphologies based on relative positions of filament ends, such as sarcomere-like organization. We found that apolar bundles show a remarkable sensitivity to environmental conditions, which may be important in enabling rapid cytoskeletal structural reorganization and adaptation in response to intracellular and extracellular cues.

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Section: Methodsmentioning

confidence: 99%

Remarkable structural transformations of actin bundles are driven by their initial polarity, motor activity, crosslinking, and filament treadmilling

2019

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“…The current simulator was developed in a 3D environment and the movement of the molecules was restricted to a 2D space for reducing the simulation complexity as we analyzed only the formation of Level 2-3 sub-structures. Considering the recommendation made by Jamie et al [19] about the effect of spatial dimensionality, we plan to extend the framework in 3D (Level 4) in the future to form complete MTs from the current substructures (Level 1-3). We also plan to include the effect of MTOCs, Golgi apparatus by adding new environments and interaction rules.…”

Section: Discussionmentioning

confidence: 99%

“…Also, the effect of several mutants destroying the self-organization was analyzed in their work. The effect of spatial dimensionality on MT self-organization was investigated by Jamie et al [19]. They conducted simulations on filament active networks and motor-proteins self-organizing into tubes in 2D and 3D spaces.…”

Section: Introductionmentioning

confidence: 99%

Mimicking Sub-Structures Self-Organization in Microtubules

Palaparthi

Pidaparti

2019

Biomimetics

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Microtubules (MTs) are highly dynamic polymers distributed in the cytoplasm of a biological cell. Alpha and beta globular proteins constituting the heterodimer building blocks combine to form these tubules through polymerization, controlled by the concentration of Guanosine-triphosphate (GTPs) and other Microtubule Associated Proteins (MAPs). MTs play a crucial role in many intracellular processes, predominantly in mitosis, organelle transport and cell locomotion. Current research in this area is focused on understanding the exclusive behaviors of self-organization and their association with different MAPs through organized laboratory experiments. However, the intriguing intelligence behind these tiny machines resulting in complex self-organizing structures is mostly unexplored. In this study, we propose a novel swarm engineering framework in modeling rules for these systems, by combining the principles of design with swarm intelligence. The proposed framework was simulated on a game engine and these simulations demonstrated self-organization of rings and protofilaments in MTs. Analytics from these simulations assisted in understanding the influence of GTPs on protofilament formation. Also, results showed that the population density of GTPs rather than their bonding probabilities played a crucial role in polymerization in forming microtubule substructures.

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“…Attractive steric forces between filaments were not included in the simulations. The steric parameters were adapted from the range in previous studies testing steric interactions between microtubules or actin filaments using Cytosim 58,59 . Because of excessive computational costs, it was difficult to perform simulations of centrosome positioning with dense actin filaments.…”

Section: Methodsmentioning

confidence: 99%

The architecture of the actin network can balance the pushing forces produced by growing microtubules

Yamamoto

Gaillard

Vianay

et al. 2022

Preprint

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The position of centrosome, the main microtubule-organizing center (MTOC), is instrumental in the definition of cell polarity. It is defined by the balance of tension and pressure forces in the network of microtubules (MTs). As MTs polymerize against the cell periphery, pressure increases and produces pushing forces on the MTOC. How the mechanical interplay between MTs and the actin network is involved in the regulation of these forces remains poorly understood, in particular because its investigation is technically limited by the structural and biochemical complexity of the cell cytoplasm. Here, in a cell-free assay, we used purified proteins to reconstitute the interaction of an aster of dynamic MTs with actin networks of various compositions and architectures in cell-sized microwells. In the absence of actin filaments, the positioning of the MTOC was highly sensitive to variations in MT length. The presence of a bulk actin filament network limited MTs deformation and displacement, and MTOCs were hold in place. In contrast, the assembly of a dense and branched actin network along the edges of the wells centered the MTOCs by preventing MT slippage and thus maintaining an isotropic balance of pushing forces. In agreement with this, an asymmetric peripheral actin network caused the MTOC to decenter by creating an asymmetry in the pushing forces. Numerical simulations demonstrated that steric hindrance by actin networks, at the tip or along the entire length of MTs, can modulate MTOC positioning, as observed in the experiments. Overall, our results show that actin networks can limit the sensitivity of MTOC positioning to MT length and enforce robust MTOC centering or decentering depending on its architecture.

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Effects of spatial dimensionality and steric interactions on microtubule-motor self-organization

Cited by 18 publications

References 50 publications

Remarkable structural transformations of actin bundles are driven by their initial polarity, motor activity, crosslinking, and filament treadmilling

Remarkable structural transformations of actin bundles are driven by their initial polarity, motor activity, crosslinking, and filament treadmilling

Mimicking Sub-Structures Self-Organization in Microtubules

The architecture of the actin network can balance the pushing forces produced by growing microtubules

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