Opposite rheological properties of neuronal microcompartments predict axonal vulnerability in brain injury

Grevesse, Thomas; Dabiri, Borna E.; Parker, Kevin Kit; Gabriele, Sylvain

doi:10.1038/srep09475

Cited by 80 publications

(70 citation statements)

References 66 publications

(74 reference statements)

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“…However, a more recent study using magnetic tweezers for local rheological measurements revealed that the soma is softer and more solid-like compared with the stiff and viscous-like neurites. The authors concluded that axons are probably more sensitive to mechanical damage than the soma 28 . However, the main load-bearing direction of neural processes is actually oriented along their length, in which elastic spring constants of a few hundred mN m −1 , viscoelastic relaxation and also active contraction have been observed [29][30][31][32][33][34] .…”

Section: Cellular Considerationsmentioning

confidence: 99%

Materials and technologies for soft implantable neuroprostheses

2016

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| Implantable neuroprostheses are engineered systems designed to restore or substitute function for individuals with neurological deficits or disabilities. These systems involve at least one uni-or bidirectional interface between a living neural tissue and a synthetic structure, through which information in the form of electrons, ions or photons flows. Despite a few notable exceptions, the clinical dissemination of implantable neuroprostheses remains limited, because many implants display inconsistent long-term stability and performance, and are ultimately rejected by the body. Intensive research is currently being conducted to untangle the complex interplay of failure mechanisms. In this Review, we emphasize the importance of minimizing the physical and mechanical mismatch between neural tissues and implantable interfaces. We explore possible materials solutions to design and manufacture neurointegrated prostheses, and outline their immense therapeutic potential. NATURE REVIEWS | MATERIALSADVANCE ONLINE PUBLICATION | 1 REVIEWS© 2 0 1 6 M a c m i l l a n P u b l i s h e r s L i m i t e d , p a r t o f S p r i n g e r N a t u r e . A l l r i g h t s r e s e r v e d .

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Section: Cellular Considerationsmentioning

confidence: 99%

Materials and technologies for soft implantable neuroprostheses

2016

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“…6,23 Briefly, magnetic beads were coated with fibronectin and incubated with patterned cells in order to bind the magnetic beads to the cytoskeleton through formation of focal adhesions. 6 A constant magnetic pulling force was applied to the beads during 12 s and the elastic modulus of living micropatterned cells was estimated with Eq. 6 by using bead displacements that were recorded with time-lapse microscopy.…”

Section: Cellular Relaxation Dynamics Is Modulated By Matrix Stiffnessmentioning

confidence: 99%

“…A home-made magnetic tweezer mounted on an inverted Nikon Eclipse Ti microscope (Nikon, Japan) and connected to a LabVIEW software (National Instruments, Austin, Texas) was positioned at a 35-degree angle to the microprinted culture substrate by using an automated micromanipulator system (InjectMan NI2, Eppendorf, Hamburg, Germany). 6 The magnetic forces were calibrated using the Stokes' law by quantifying the beads displacements in a 99% glycerol solution as a function of the current intensity and the bead-tip distance. A constant pulling force, F, was then applied to paramagnetic beads of section S and radius R bounded to the cytoskeleton of the micropatterned endothelial cells.…”

Section: Measurement Of Cell Stiffness By Magnetic Tweezersmentioning

confidence: 99%

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Probing cytoskeletal pre-stress and nuclear mechanics in endothelial cells with spatiotemporally controlled (de-)adhesion kinetics on micropatterned substrates

Versaevel

Riaz

Corne

et al. 2016

Cell Adhesion & Migration

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The mechanical properties of living cells reflect their propensity to migrate and respond to external forces. Both cellular and nuclear stiffnesses are strongly influenced by the rigidity of the extracellular matrix (ECM) through reorganization of the cyto-and nucleoskeletal protein connections. Changes in this architectural continuum affect cell mechanics and underlie many pathological conditions. In this context, an accurate and combined quantification of the mechanical properties of both cells and nuclei can contribute to a better understanding of cellular (dys-) function. To address this challenge, we have established a robust method for probing cellular and nuclear deformation during spreading and detachment from micropatterned substrates. We show that (de-)adhesion kinetics of endothelial cells are modulated by substrate stiffness and rely on the actomyosin network. We combined this approach with measurements of cell stiffness by magnetic tweezers to show that relaxation dynamics can be considered as a reliable parameter of cellular prestress in adherent cells. During the adhesion stage, large cellular and nuclear deformations occur over a long time span (>60 min). Conversely, nuclear deformation and condensed chromatin are relaxed in a few seconds after detachment. Finally, our results show that accumulation of farnesylated prelamin leads to modifications of the nuclear viscoelastic properties, as reflected by increased nuclear relaxation times. Our method offers an original and non-intrusive way of simultaneously gauging cellular and nuclear mechanics, which can be extended to high-throughput screens of pathological conditions and potential countermeasures.

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“…However, the question of the mechanical vulnerability of the axon over the soma remained misunderstood. We addressed this issue by combining microcontact printing and magnetic tweezers to apply local stresses on paramagnetic beads bound to individual microcompartments of bipolar cortical neurons and measured the creep response [29] . Our results indicate that the axon is characterized by a pronounced viscous state, while the soma behaves like an elastic solid (Fig.…”

Section: Research Highlightmentioning

confidence: 99%

Dissecting the mechanical behavior of neuronal microcompartments by combining magnetic tweezers and protein micropatterns

Grevesse¹,

Lantoine²,

Delhaye³

et al. 2016

Neurosci Commun

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Alterations of the axonal morphology are key signatures of traumatic brain injury (TBI). Although the pathobiology of axonal injury has been extensively investigated, the vulnerability of the axonal microcompartment over the soma was still misunderstood. We hypothesized that the soma and the axon of neurons display opposite mechanical behaviors, rendering the axon more sensitive to a mechanical stress. To test this hypothesis, we used a microcontact printing method to control the growth of cortical neuron in a bipolar morphology and the viscoelastic properties of soma and axon microcompartments were measured with magnetic tweezers. Creep experiments showed that neuronal microcompartments exhibit distinct mechanical behaviors: the soma is softer and characterized by an elastic-like behavior, while the neurite is stiffer and viscous-like. By altering cytoskeletal filaments with pharmacological agents, we determined the origin of the compartmentalization of mechanical behaviors within cortical neurons. The nucleus determines the elastic and stress stiffening behavior of the soma, while the sliding of neurofilaments determines the viscous-like state of the neurite. In addition, our results revealed that at the contrary of the soma, the neurite can sense its mechanical environment and becomes softer and more viscous on soft surfaces, showing that, as for the mechanical behavior, the mechanosensitivity is localized to the neuronal microcompartments. Our findings shed light on the importance of the regionalization of neuronal properties to their microcompartments in response to a mechanical insult. Future works will need to investigate the relationship between the mechanical differences of neuronal microcompartments and their functions. In this context, we suggest to consider microprinted neuronal networks as an efficient tool for investigating the effect of the propagation of injury forces on the behavior of neuronal circuits.Keywords: Neuron; microcompartment; rheology; diffuse axonal injury; mechanosensitivity To cite this article: Thomas Grevesse, et al. Dissecting the mechanical behavior of neuronal microcompartments by combining magnetic tweezers and protein micropatterns. Neurosci Commun 2015; 1: e1003.

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Opposite rheological properties of neuronal microcompartments predict axonal vulnerability in brain injury

Cited by 80 publications

References 66 publications

Materials and technologies for soft implantable neuroprostheses

Materials and technologies for soft implantable neuroprostheses

Probing cytoskeletal pre-stress and nuclear mechanics in endothelial cells with spatiotemporally controlled (de-)adhesion kinetics on micropatterned substrates

Dissecting the mechanical behavior of neuronal microcompartments by combining magnetic tweezers and protein micropatterns

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