Modeling of the mechano-chemical behaviour of the nuclear pore complex: current research and perspectives

García, A.; Matas, José Félix Rodríguez; Raimondi, Manuela Teresa

doi:10.1039/c6ib00153j

Cited by 16 publications

(20 citation statements)

References 92 publications

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“…In the case of a full blockage of the NPC due to high trafficking and deformation, it therefore allows the ions to open the distal ring and thus, to increase the flux through the NPC. We already mentioned this in a previous paper (Garcia et al, 2016 ) and referenced the works of (Maimon et al, 2012 ; Eibauer et al, 2015 ) which showed such secondary channels.…”

Section: Discussionmentioning

confidence: 70%

“…NPCs are a substructure assembly composed of several coaxial rings and 8-fold rotational (Goldberg and Allen, 1996 ; Beck et al, 2004 ; Löschberger et al, 2012 ) symmetrical structures named according to their spatial location: (1) The cytoplasmic ring (CR) and filaments in the cytoplasmic side; (2) The spoke ring (SR) and transmembrane ring, which provide stiffness and stability to the complete NPC, in the nuclear envelop; (3) The nuclear ring (NR), which is attached to the lamina, the nuclear basket, and the distal ring (DR) in the nuclear side. For a detailed description of the structure of the NPC, see the review paper (Garcia et al, 2016 ).…”

Section: Introductionmentioning

confidence: 99%

“…(B) Main sub-structural groups (rings, filaments, and basket) that make up an NPC. (Reproduced from Garcia et al, 2016 with permission from the Royal Society of Chemistry).…”

Section: Introductionmentioning

confidence: 99%

“…Computational modeling of nuclear diffusion-deformation phenomena entails coupling structural mechanics models for the NE and NPC with diffusion equations for the transcription factors, which is an essentially unexplored field. Few published examples of numerical simulations address the mechanics of the NPC and its effect on nucleocytoplasmic transport (reviewed in Garcia et al, 2016 ). At the cell scale, our group developed a finite element simulation of passive diffusive fluxes from the cytoplasm to the nucleus, accounting for nuclear deformation (Nava et al, 2015a ).…”

Section: Introductionmentioning

confidence: 99%

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The Effect of Cell Morphology on the Permeability of the Nuclear Envelope to Diffusive Factors

et al. 2018

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A recent advance in understanding stem cell differentiation is that the cell is able to translate its morphology, i.e., roundish or spread, into a fate decision. We hypothesize that strain states in the nuclear envelope (NE) cause changes in the structure of the nuclear pore complexes. This induces significant changes in the NE's permeability to the traffic of the transcription factors involved in stem cell differentiation which are imported into the nucleus by passive diffusion. To demonstrate this, we set up a numerical model of the transport of diffusive molecules through the nuclear pore complex (NPC), on the basis of the NPC deformation. We then compared the prediction of the model for two different cell configurations with roundish and spread nuclear topologies with those measured on cells cultured in both configurations. To measure the geometrical features of the NPC, using electron tomography we reconstructed three-dimensional portions of the envelope of cells cultured in both configurations. We found non-significant differences in both the shape and size of the transmembrane ring of single pores with envelope deformation. In the numerical model, we thus assumed that the changes in pore complex permeability, caused by the envelope strains, are due to variations in the opening configuration of the nuclear basket, which in turn modifies the porosity of the pore complex mainly on its nuclear side. To validate the model, we cultured cells on a substrate shaped as a spatial micro-grid, called the “nichoid,” which is nanoengineered by two-photon laser polymerization, and induces a roundish nuclear configuration in cells adhering to the nichoid grid, and a spread configuration in cells adhering to the flat substrate surrounding the grid. We then measured the diffusion through the nuclear envelope of an inert green-fluorescent protein, by fluorescence recovery after photobleaching (FRAP). Finally, we compared the diffusion times predicted by the numerical model for roundish vs. spread cells, with the measured times. Our data show that cell stretching modulates the characteristic time needed for the nuclear import of a small inert molecule, GFP, and the model predicts a faster import of diffusive molecules in the spread compared to roundish cells.

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Section: Discussionmentioning

confidence: 70%

Section: Introductionmentioning

confidence: 99%

“…(B) Main sub-structural groups (rings, filaments, and basket) that make up an NPC. (Reproduced from Garcia et al, 2016 with permission from the Royal Society of Chemistry).…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The Effect of Cell Morphology on the Permeability of the Nuclear Envelope to Diffusive Factors

et al. 2018

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“…Beyond the direct force propagation via the extracellular matrix–cytoskeleton–nuclear envelope continuum, mechanotransduction also occurs through more indirect ways. For instance, nuclear pore size may be modified in response to nuclear envelope stretching (Garcia et al 2016 ). Alternatively, nuclear membrane may convert tension into biochemical signals, notably by mediating store release of Ca 2+ at the outer nuclear membrane through mechanosensitive ion channels.…”

Section: Conclusion: Avenues For Future Research In Plantsmentioning

confidence: 99%

Nuclear envelope: a new frontier in plant mechanosensing?

et al. 2017

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In animals, it is now well established that forces applied at the cell surface are propagated through the cytoskeleton to the nucleus, leading to deformations of the nuclear structure and, potentially, to modification of gene expression. Consistently, altered nuclear mechanics has been related to many genetic disorders, such as muscular dystrophy, cardiomyopathy and progeria. In plants, the integration of mechanical signals in cell and developmental biology has also made great progress. Yet, while the link between cell wall stresses and cytoskeleton is consolidated, such cortical mechanical cues have not been integrated with the nucleoskeleton. Here, we propose to take inspiration from studies on animal nuclei to identify relevant methods amenable to probing nucleus mechanics and deformation in plant cells, with a focus on microrheology. To identify potential molecular targets, we also compare the players at the nuclear envelope, namely lamina and LINC complex, in both plant and animal nuclei. Understanding how mechanical signals are transduced to the nucleus across kingdoms will likely have essential implications in development (e.g. how mechanical cues add robustness to gene expression patterns), in the nucleoskeleton–cytoskeleton nexus (e.g. how stress is propagated in turgid/walled cells), as well as in transcriptional control, chromatin biology and epigenetics.

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Mechanical regulation of nucleocytoplasmic translocation in mesenchymal stem cells: characterization and methods for investigation

et al. 2019

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Mesenchymal stem cells (MSCs) have immune-modulatory and tissue-regenerative properties that make them a suitable and promising tool for cell-based therapy application. Since the bio-chemo-mechanical environment influences MSC fate and behavior, the understanding of the mechanosensors involved in the transduction of mechanical inputs into chemical signals could be pivotal. In this context, the nuclear pore complex is a molecular machinery that is believed to have a key role in force transmission and in nucleocytoplasmic shuttling regulation. To fully understand the nuclear pore complex role and the nucleocytoplasmic transport dynamics, recent advancements in fluorescence microscopy provided the possibility to study passive and facilitated nuclear transports also in mechanically stimulated cell culture conditions. Here, we review the current available methods for the investigation of nucleocytoplasmic shuttling, including photo-perturbation-based approaches, fluorescence correlation spectroscopy, and single-particle tracking techniques. For each method, we analyze the advantages, disadvantages, and technical limitations. Finally, we summarize the recent knowledge on mechanical regulation of nucleocytoplasmic translocation in MSC, the relevant progresses made so far, and the future perspectives in the field.

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Modeling of the mechano-chemical behaviour of the nuclear pore complex: current research and perspectives

Abstract: This review opens the door to the consideration of how mechanosensing and mechanotransduction can affect the nanomechanics of the NPC.

Cited by 16 publications

References 92 publications

The Effect of Cell Morphology on the Permeability of the Nuclear Envelope to Diffusive Factors

The Effect of Cell Morphology on the Permeability of the Nuclear Envelope to Diffusive Factors

Nuclear envelope: a new frontier in plant mechanosensing?

Mechanical regulation of nucleocytoplasmic translocation in mesenchymal stem cells: characterization and methods for investigation

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