Viscoelastic properties of white and gray matter-derived microglia differentiate upon treatment with lipopolysaccharide but not upon treatment with myelin.

BACKGROUND: The biomechanical properties of the brain have increasingly been shown to relate to brain pathology in neurological diseases, including multiple sclerosis (MS). Inflammation and demyelination in MS induce significant changes in brain stiffness which can be linked to the relative abundance of glial cells in lesions. We hypothesize that the biomechanical, in addition to biochemical, properties of white (WM) and gray matter (GM)-derived microglia may contribute to the differential microglial phenotypes as seen in MS WM and GM lesions. METHODS: Primary glial cultures from WM or GM of rat adult brains were treated with either lipopolysaccharide (LPS), myelin, or myelin+LPS for 24 h or left untreated as a control. After treatment, microglial cells were indented using dynamic indentation to determine the storage and loss moduli reflecting cell elasticity and cell viscosity, respectively, and subsequently fixed for immunocytochemical analysis. In parallel, gene expression of inflammatory-related genes were measured using semi-quantitative RT-PCR. Finally, phagocytosis of myelin was determined as well as F-actin visualized to study the cytoskeletal changes. RESULTS: WM-derived microglia were significantly more elastic and more viscous than microglia derived from GM. This heterogeneity in microglia biomechanical properties was also apparent when treated with LPS when WM-derived microglia decreased cell elasticity and viscosity, and GM-derived microglia increased elasticity and viscosity. The increase in elasticity and viscosity observed in GM-derived microglia was accompanied by an increase in Tnfα mRNA and reorganization of F-actin which was absent in WM-derived microglia. In contrast, when treated with myelin, both WM- and GM-derived microglia phagocytose myelin decrease their elasticity and viscosity. CONCLUSIONS: In demyelinating conditions, when myelin debris is phagocytized, as in MS lesions, it is likely that the observed differences in WM- versus GM-derived microglia biomechanics are mainly due to a difference in response to inflammation, rather than to the event of demyelination itself. Thus, the differential biomechanical properties of WM and GM microglia may add to their differential biochemical properties which depend on inflammation present in WM and GM lesions of MS patients.

70 µm diameter optical probe for common-path optical coherence tomography in air and liquids.

We investigate and validate a novel method to fabricate ultrathin optical probes for common-path optical coherence tomography (CP-OCT). The probes are obtained using a 65 µm barium titanate microsphere inserted into an inward concave cone chemically etched at the end of a single-mode fiber. We demonstrate that the high refractive index (n=1.95) of the barium titanate microspheres allows one to maintain high sensitivity even while imaging in liquids, reaching a sensitivity of 83 dB. Due to its low cost, flexibility, and ease of use, the probe holds promise for the development of a new generation of ultrathin needle-based OCT systems.

A Traumatic Impact Immediately Changes the Mechanical Properties of Articular Cartilage.

OBJECTIVE: To investigate whether and how a single traumatic impact changes the mechanical properties of talar articular cartilage. DESIGN: A marble was placed on the joint surface and a weight was dropped on both medial and lateral caprine talus to create a well-defined single focal impact. The mechanical properties of intact and impacted talar cartilage were measured with a micro-indenter. Elastic (storage) and viscous (loss) moduli were determined by oscillatory ramp and dynamic mechanical analysis protocols. RESULTS: We found significant differences between ankles and within the same ankle joint, with the medial talus having significantly higher storage- and loss moduli than the lateral talus. The storage- and loss moduli of intact articular cartilage increased with greater indentation depths. However, postimpact the storage- and loss moduli were significantly and consistently lower in all specimens indicating immediate posttraumatic damage. The deeper regions of talar cartilage were less affected by the impact than the more superficial regions. CONCLUSIONS: A single traumatic impact results in an immediate and significant decrease of storage- and loss moduli. Further research must focus on the development of non- or minimally invasive diagnostic tools to address the exact microdamage caused by the impact. We speculate that the traumatic impact damaged the collagen fibers that confine the water-binding proteoglycans and thereby decreasing the hydrostatic pressure of cartilage. As part of the treatment directly after a trauma, one could imagine a reduction or restriction of peak loads to prevent the progression of the cascade towards PTOA of the ankle joint.

Mapping the mechanical properties of paintings via nanoindentation: a new approach for cultural heritage studies.

A comprehensive understanding of the behaviour of the heterogenous layers within the paint stratigraphies in historical paintings is crucial to evaluate their long term stability. We aim to refine nanoindentation as a new tool to investigate the mechanical behaviour of historical oil paints, by adapting the probes and the protocol already used in biomechanical research on soft tissues. The depth-controlled indentation profile performed with a spherical probe provides an evaluation of the non-linear viscoelastic behaviour of the individual layers in paint at local scale. The technique is non-destructive and guarantees the integrity of the surface after indentation. The mapping of elasticity demonstrates the properties' heterogeneity of the composite material within the paint layers, as well as between the individual layers and their interfaces.

Dynamic indentation reveals differential viscoelastic properties of white matter versus gray matter-derived astrocytes upon treatment with lipopolysaccharide.

Astrocytes in white matter (WM) and gray matter (GM) brain regions have been reported to have different morphology and function. Previous single cell biomechanical studies have not differentiated between WM- and GM-derived samples. In this study, we explored the local viscoelastic properties of isolated astrocytes and show that astrocytes from rat brain WM-enriched areas are ~1.8 times softer than astrocytes from GM-enriched areas. Upon treatment with pro-inflammatory lipopolysaccharide, GM-derived astrocytes become significantly softer in the nuclear and the cytoplasmic regions, where the F-actin network appears rearranged, whereas WM-derived astrocytes preserve their initial mechanical features and show no alteration in the F-actin cytoskeletal network. We hypothesize that the flexibility in biomechanical properties of GM-derived astrocytes may contribute to promote regeneration of the brain under neuroinflammatory conditions.