Lamellar and fibre bundle mechanics of the annulus fibrosus in bovine intervertebral disc

ArticleThe intervertebral disc is a multicomposite structure, with an outer fibrous ring, the annulus fibrosus, retaining a gel-like core, the nucleus pulposus. The disc presents complex mechanical behaviour, and it is of high importance for spine biomechanics. Advances in multiscale modelling and disc repair raised a need for new quantitative data on the finest details of annulus fibrosus mechanics. In this work we explored inter-lamella and inter-bundle behaviour of the outer annulus using micromechanical testing and second harmonic generation microscopy. Twenty-one intervertebral discs were dissected from cow tails; the nucleus and inner annulus were excised to leave a ring of outer annulus, which was tested in circumferential loading while imaging the tissue’s collagen fibres network with sub-micron resolution. Custom software was developed to determine local tissue strains through image analysis. Inter-bundle linear and shear strains were 5.5 and 2.8 times higher than intra-bundle strains. Bundles tended to remain parallel while rotating under loading, with large slipping between them. Inter-lamella linear strain was almost 3 times the intra-lamella one, but no slipping was observed at the junction between lamellae. This study confirms that outer annulus straining is mainly due to bundles slipping and rotating. Further development of disc multiscale modelling and repair techniques should take into account this modular behaviour of the lamella, rather than considering it as a homogeneous fibre-reinforced matrix.Henry Smith Charit

The micromechanics of the superficial zone of articular cartilage.

Journal ArticleOBJECTIVE: To investigate the relationships between the unique mechanical and structural properties of the superficial zone of articular cartilage on the microscopic scale. DESIGN: Fresh unstained equine metacarpophalangeal cartilage samples were mounted on tensile and compressive loading rigs on the stage of a multiphoton microscope. Sequential image stacks were acquired under incremental loads together with simultaneous measurements of the applied stress and strain. Second harmonic generation was used to visualise the collagen fibre network, while two photon fluorescence was used to visualise elastin fibres and cells. The changes visualised by each modality were tracked between successive loads. RESULTS: The deformation of the cartilage matrix was heterogeneous on the microscopic length scale. This was evident from local strain maps, which showed shearing between different regions of collagen under tensile strain, corrugations in the articular surface at higher tensile strains and a non-uniform distribution of compressive strain in the axial direction. Chondrocytes elongated and rotated under tensile strain and were compressed in the axial direction under compressive load. The magnitude of deformation varied between cells, indicating differences in either load transmission through the matrix or the mechanical properties of individual cells. Under tensile loading the reorganisation of the elastin network differed from a homogeneous elastic response, indicating that it forms a functional structure. CONCLUSIONS: This study highlights the complexity of superficial zone mechanics and demonstrates that the response of the collagen matrix, elastin fibres and chondrocytes are all heterogeneous on the microscopic scale.Arthritis Research U

Effect of hydroperoxides on red blood cell membrane mechanical properties

Copyright © 2011 Biophysical SocietyWe investigate the effect of oxidative stress on red blood cell membrane mechanical properties in vitro using detailed analysis of the membrane thermal fluctuation spectrum. Two different oxidants, the cytosol-soluble hydrogen peroxide and the membrane-soluble cumene hydroperoxide, are used, and their effects on the membrane bending elastic modulus, surface tension, strength of confinement due to the membrane skeleton, and 2D shear elastic modulus are measured. We find that both oxidants alter significantly the membrane elastic properties, but their effects differ qualitatively and quantitatively. While hydrogen peroxide mainly affects the elasticity of the membrane protein skeleton (increasing the membrane shear modulus), cumene hydroperoxide has an impact on both membrane skeleton and lipid bilayer mechanical properties, as can be seen from the increased values of the shear and bending elastic moduli. The biologically important implication of these results is that the effects of oxidative stress on the biophysical properties, and hence the physiological functions, of the cell membrane depend on the nature of the oxidative agent. Thermal fluctuation spectroscopy provides a means of characterizing these different effects, potentially in a clinical milieu

Ferromagnetic microswimmers

Copyright © 2008 The American Physical SocietyWe propose a model for a novel artificial low Reynolds number swimmer, based on the magnetic interactions of a pair of ferromagnetic particles: one with hard and the other with soft magnetic properties, connected by a linear spring. Using a computational model, we analyze the behavior of the system and demonstrate that for realistic values of the parameters involved, the swimmer is capable of self-propelling with average speeds of the order of hundreds of micrometers per second

Chemically specific imaging and in-situ chemical analysis of articular cartilage with stimulated Raman scattering

This is the pre-peer reviewed version of the following article: Mansfield, J., Moger, J., Green, E., Moger, C. and Winlove, C. P. (2013), Chemically specific imaging and in-situ chemical analysis of articular cartilage with stimulated Raman scattering. J. Biophoton., 6: 803–814. doi: 10.1002/jbio.201200213, which has been published in final form at http://dx.doi.org/10.1002/jbio.201200213.© 2013 by WILEY-VCH Verlag GmbH & Co. KGaA, WeinheimStimulated Raman scattering (SRS) has been applied to unstained samples of articular cartilage enabling the investigation of living cells within fresh tissue. Hyperspectral SRS measurements over the CH vibrational region showed variations in protein and lipid content within the cells, pericellular matrix and interterritorial matrix. Changes in the cells and pericellular matrix were investigated as a function of depth into the cartilage. Lipid was detected in the pericellular matrix of superficial zone chondrocytes. The spectral profile of lipid droplets within the chondrocytes indicated that they contained predominantly unsaturated lipids. The mineral content has been imaged by using the PO₄³⁻ vibration at 959 cm⁻¹ and the CO₃²⁻ vibration at 1070 cm⁻¹. Both changes in cells and mineralization are known to be important factors in the progression of osteoarthritis. SRS enables these to be visualized in fresh unstained tissue and consequently should benefit osteoarthiritis research

The structure and micromechanics of elastic tissue.

Journal ArticleReviewElastin is a major component of tissues such as lung and blood vessels, and endows them with the long-range elasticity necessary for their physiological functions. Recent research has revealed the complexity of these elastin structures and drawn attention to the existence of extensive networks of fine elastin fibres in tissues such as articular cartilage and the intervertebral disc. Nonlinear microscopy, allowing the visualization of these structures in living tissues, is informing analysis of their mechanical properties. Elastic fibres are complex in composition and structure containing, in addition to elastin, an array of microfibrillar proteins, principally fibrillin. Raman microspectrometry and X-ray scattering have provided new insights into the mechanisms of elasticity of the individual component proteins at the molecular and fibrillar levels, but more remains to be done in understanding their mechanical interactions in composite matrices. Elastic tissue is one of the most stable components of the extracellular matrix, but impaired mechanical function is associated with ageing and diseases such as atherosclerosis and diabetes. Efforts to understand these associations through studying the effects of processes such as calcium and lipid binding and glycation on the mechanical properties of elastin preparations in vitro have produced a confusing picture, and further efforts are required to determine the molecular basis of such effects.British Heart FoundationArthritis U

Theory of ferromagnetic microswimmers

Copyright © 2011 Oxford University Press. This is a pre-copy-editing, author-produced PDF of an article accepted for publication in The Quarterly Journal of Mechanics and Applied Mathematics following peer review. The definitive publisher-authenticated version [Volume 64, Issue 3, pp. 239-263] is available online at: http://qjmam.oxfordjournals.org/content/64/3/239This paper considers the dynamics of a microscale swimmer based on two magnetic beads that are elastically coupled together. A time-varying external magnetic field is imposed that has two principal effects: one is to exert a torque on the magnetic beads. The second is to change the orientation of the magnetic field dipoles in one or both beads, depending on their ferromagnetic properties. This then creates an attraction or repulsion between the two dipoles. The combination of dipole attraction/repulsion, moderated by the elastic coupling, and torque gives motions that are not generally time reversible and can lead to unidirectional swimming, that is persistent motion in one direction, in a Stokes flow regime. The equations of motion for the swimmer are set up using a Lagrangian formulation and supplemented by equations giving the dipole orientation of the magnetic fields of the beads in the external field. The equations are non-dimensionalized and key parameters determined. Numerical simulations reveal a number of regimes that are studied using simplified models and multiple scale analysis. Approximate thresholds are obtained above which the swimmer moves in a closed path and below which the orientation is `trapped' giving unidirectional motion. Three mechanisms for such trapping are isolated and discussed

Alcohol consumption among university students in the night-time economy in the UK: A three-wave longitudinal study

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this recordBackground. Excessive alcohol consumption is commonly reported in university/college students, and contributes to emerging peer-group relations. Purpose. This study aimed to provide up-to-date longitudinal data on students’ alcohol consumption patterns, and predictors of this, across a single academic year. Methods. A 3-wave study was conducted at a university in the UK. Participants reported their alcohol consumption patterns, along with perceptions of the social norms and behavioral expectations associated with attending licensed venues where alcohol is sold (the “night time economy”). Participants also reported their social identification with this environment. Results. Around half of participants overall fell into the three higher alcohol-risk categories (moderate, high or hazardous drinking). A modest reduction in consumption was observed across the study. At each assessment point, males reported greater alcohol consumption in the preceding two months than females, while Year 4 students and those on graduate-entry programs reported the lowest consumption. Excessive alcohol consumption was regarded as largely normative within the night time economy, both descriptively (“what others do”) and injunctively (“what others approve of”). Social identification and norm perceptions, along with gender, year group, and intoxication and socialising expectations, were significantly associated with higher alcohol consumption at baseline. However, baseline consumption was the only variable significantly associated with alcohol use at the end of the academic year. Conclusions. Many students drink alcohol at potentially harmful levels, and norms and expectations supporting this consumption are prominent and stable. The findings support a targeted approach to intervention that accounts for heterogeneity in the student population.Drinkaware TrustNational Institute for Health Research (NIHR

Red blood cell thermal fluctuations: comparison between experiment and molecular dynamics simulations

Copyright © 2013 Royal Society of ChemistryWe outline a new method of analysis of thermal shape fluctuations of red blood cells, based on comparison between experiments and coarse-grained molecular dynamics simulations. The fluctuations of 2D equatorial contours of red blood cells are recorded experimentally using fast phase-contrast video microscopy, from which the fluctuation spectrum is calculated. The spectrum is compared to the corresponding contour fluctuation spectrum obtained from a finite-temperature particle-dynamics simulation, modelling a cell with bending and shear elasticity and conserved volume and surface area. We demonstrate that the simulation correctly describes the mean cell shape as well as the membrane thermal fluctuations, returning physically sound values for the relevant membrane elastic moduli

The neural correlates of visual imagery vividness - an fMRI study and literature review

This is the final version of the article. Available from Elsevier via the DOI in this record.Using the Vividness of Visual Imagery Questionnaire we selected 14 high-scoring and 15 low-scoring healthy participants from an initial sample of 111 undergraduates. The two groups were matched on measures of age, IQ, memory and mood but differed significantly in imagery vividness. We used fMRI to examine brain activation while participants looked at, or later imagined, famous faces and famous buildings. Group comparison revealed that the low-vividness group activated a more widespread set of brain regions while visualising than the high-vividness group. Parametric analysis of brain activation in relation to imagery vividness across the entire group of participants revealed distinct patterns of positive and negative correlation. In particular, several posterior cortical regions show a positive correlation with imagery vividness: regions of the fusiform gyrus, posterior cingulate and parahippocampal gyri (BAs 19, 29, 31 and 36) displayed exclusively positive correlations. By contrast several frontal regions including parts of anterior cingulate cortex (BA 24) and inferior frontal gyrus (BAs 44 and 47), as well as the insula (BA 13), auditory cortex (BA 41) and early visual cortices (BAs 17 and 18) displayed exclusively negative correlations. We discuss these results in relation to a previous, functional imaging study of a clinical case of ‘blind imagination’, and to the existing literature on the functional imaging correlates of imagery vividness and related phenomena in visual and other domains.Jonathan Fulford’s salary was supported via an NIHR grant