Effects of the cross-linkers on the buckling of microtubules in cells

Li, Si; Wang, Chengyuan; Nithiarasu, Perumal

doi:10.1016/j.jbiomech.2018.03.002

Cited by 7 publications

(5 citation statements)

References 34 publications

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“…Mathematical models support MT-MT cross-linkage as an important structural feature of axons (e.g. [310–313]), and physical cross-linking strands of varying length between axonal MTs were observed decades ago [16, 314]. Such MT-MT cross-linkers would be expected to detach upon super-threshold pull or compression, and re-attach thereafter (Fig.…”

Section: Potential Roles Of Mt-mt Cross-linkage In Mt Bundle Maintenancementioning

confidence: 99%

The model of local axon homeostasis - explaining the role and regulation of microtubule bundles in axon maintenance and pathology

et al. 2019

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Axons are the slender, cable-like, up to meter-long projections of neurons that electrically wire our brains and bodies. In spite of their challenging morphology, they usually need to be maintained for an organism's lifetime. This makes them key lesion sites in pathological processes of ageing, injury and neurodegeneration. The morphology and physiology of axons crucially depends on the parallel bundles of microtubules (MTs), running all along to serve as their structural backbones and highways for life-sustaining cargo transport and organelle dynamics. Understanding how these bundles are formed and then maintained will provide important explanations for axon biology and pathology. Currently, much is known about MTs and the proteins that bind and regulate them, but very little about how these factors functionally integrate to regulate axon biology. As an attempt to bridge between molecular mechanisms and their cellular relevance, we explain here the model of local axon homeostasis, based on our own experiments in Drosophila and published data primarily from vertebrates/mammals as well as C. elegans. The model proposes that (1) the physical forces imposed by motor protein-driven transport and dynamics in the confined axonal space, are a life-sustaining necessity, but pose a strong bias for MT bundles to become disorganised. (2) To counterbalance this risk, MT-binding and-regulating proteins of different classes work together to maintain and protect MT bundles as necessary transport highways. Loss of balance between these two fundamental processes can explain the development of axonopathies, in particular those linking to MT-regulating proteins, motors and transport defects. With this perspective in mind, we hope that more researchers incorporate MTs into their work, thus enhancing our chances of deciphering the complex regulatory networks that underpin axon biology and pathology.

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Section: Potential Roles Of Mt-mt Cross-linkage In Mt Bundle Maintenancementioning

confidence: 99%

The model of local axon homeostasis - explaining the role and regulation of microtubule bundles in axon maintenance and pathology

et al. 2019

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“…A constant radial orientation was proposed to be associated with higher critical load and 3D buckling means, while the diversity of axial density resulted in localized buckling. These data suggest that the process by which cross‐linkers regulate MT stiffness involves a combination of ordered and less‐ordered processes occurring in parallel (Li et al, ).…”

Section: Randomness In Mt Structurementioning

confidence: 96%

Randomness in microtubule dynamics: an error that requires correction or an inherent plasticity required for normal cellular function?

Ilan

2019

Cell Biology International

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Microtubules (MTs) play roles in regulating the mechanical structure and dynamics of cells. While MTs appear to be highly ordered structures, recent data suggest some randomness in their structure and dynamics. Part of this inherent randomness is attributed to errors and correction mechanisms are being investigated to overcome these ‘mistakes.’ However, this randomness may also be part of the normal intracellular function of MTs. It is possible that random events in MT structure and dynamics may contribute to their normal function and may even be part of an improved efficacy mechanism. An alternative view, wherein MT and kinetochore errors are part of required cell plasticity, is also discussed. These data may further support the concept of randomness in biological pathways as part of self‐organization or accurate and enhanced function.

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“…The technique established the equivalency between the deformations of the structure of MTs and the structural frame representation of MTs. Its robustness and efficiency have been demonstrated in studying the mechanical responses of MTs such as vibration and buckling 43,66–70 . Specifically, the MSM models with monomeric feature were employed to identify the origin of the inter‐PF sliding and its role in bending and vibration of MTs 43 .…”

Section: Protein Filament Modelsmentioning

confidence: 99%

“…A 3D transverse vibration was reported for MTs, where the bending axis of the cross‐section rotates along the longitudinal direction and each half‐wave oscillates in different planes 68 . The MSM model was also used to explore the subcellular environment effect on the MT mechanics and reveal the physics of the experimentally observed localized buckling as well as the role of the cross‐linker in determining MT stiffness 69 . Moreover, studies were carried out using the MSM model for MT vibration excited by an alternating external electric field which provides useful guidance to the development of the MT‐based biosensors 71–72 …”

Section: Protein Filament Modelsmentioning

confidence: 99%

Biomechanics of cells and subcellular components: A comprehensive review of computational models and applications

Wang

Ademiloye

et al. 2021

Numer Methods Biomed Eng

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Cells are a fundamental structural, functional and biological unit for all living organisms. Up till now, considerable efforts have been made to study the responses of single cells and subcellular components to an external load, and understand the biophysics underlying cell rheology, mechanotransduction and cell functions using experimental and in silico approaches. In the last decade, computational simulation has become increasingly attractive due to its critical role in interpreting experimental data, analysing complex cellular/subcellular structures, facilitating diagnostic designs and therapeutic techniques, and developing biomimetic materials. Despite the significant progress, developing comprehensive and accurate models of living cells remains a grand challenge in the 21st century. To understand current state of the art, this review summarises and classifies the vast array of computational biomechanical models for cells. The article covers the cellular components at multi‐spatial levels, that is, protein polymers, subcellular components, whole cells and the systems with scale beyond a cell. In addition to the comprehensive review of the topic, this article also provides new insights into the future prospects of developing integrated, active and high‐fidelity cell models that are multiscale, multi‐physics and multi‐disciplinary in nature. This review will be beneficial for the researchers in modelling the biomechanics of subcellular components, cells and multiple cell systems and understanding the cell functions and biological processes from the perspective of cell mechanics.

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Effects of the cross-linkers on the buckling of microtubules in cells

Cited by 7 publications

References 34 publications

The model of local axon homeostasis - explaining the role and regulation of microtubule bundles in axon maintenance and pathology

The model of local axon homeostasis - explaining the role and regulation of microtubule bundles in axon maintenance and pathology

Randomness in microtubule dynamics: an error that requires correction or an inherent plasticity required for normal cellular function?

Biomechanics of cells and subcellular components: A comprehensive review of computational models and applications

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