Quantifying collagen fibre architecture in articular cartilage using small-angle X-ray scattering

Tadimalla, Sirisha; Tourell, Monique C.; Knott, Robert; Momot, Konstantin I.

doi:10.3233/bsi-170164

Cited by 11 publications

(8 citation statements)

References 44 publications

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“…More specifically, previous groups have quantified both spatially resolved fibrillar orientation [32], [33] as well as nanostructural parameters such as the D-periodicity and inter-fibrillar spacing in biological tissues such as bone and tendon [34], [35], [36], [37]. However there have been far fewer studies utilising X-ray diffraction in determining such parameters in cartilage [20], [38]. Our previous work [20] showed that SAXS could pick up transient changes in fibrillar pre-strain in the deep zone of AC during macroscopic stress-relaxation.…”

Section: Introductionmentioning

confidence: 99%

Proteoglycan degradation mimics static compression by altering the natural gradients in fibrillar organisation in cartilage

et al. 2019

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Section: Introductionmentioning

confidence: 99%

Proteoglycan degradation mimics static compression by altering the natural gradients in fibrillar organisation in cartilage

et al. 2019

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“…Tropocollagen molecules self-assemble, through a combination of covalent and electrostatic interactions, into fibres. The assembly has a 67 nm stagger, which gives collagen fibres their characteristic banding in electron micrographs and the Bragg reflections in small-angle X-ray scattering, along with a characteristic and predictable pattern in 2 nd harmonic generation microscopy [ 29 , 30 ]. Collagen fibres form a cross-linked network and it is this network that gives the ECM its tensile strength ; serving as a three-dimensional (3D)scaffold that anchors GAG and PG molecules, forming the structural core of the ECM and holding it together.…”

Section: Biophysical Basis Of the Mechanical Properties Of Breast Tissuementioning

confidence: 99%

Mechanical Pressure Driving Proteoglycan Expression in Mammographic Density: a Self-perpetuating Cycle?

Reye

Huang

Haupt

et al. 2021

J Mammary Gland Biol Neoplasia

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Regions of high mammographic density (MD) in the breast are characterised by a proteoglycan (PG)-rich fibrous stroma, where PGs mediate aligned collagen fibrils to control tissue stiffness and hence the response to mechanical forces. Literature is accumulating to support the notion that mechanical stiffness may drive PG synthesis in the breast contributing to MD. We review emerging patterns in MD and other biological settings, of a positive feedback cycle of force promoting PG synthesis, such as in articular cartilage, due to increased pressure on weight bearing joints. Furthermore, we present evidence to suggest a pro-tumorigenic effect of increased mechanical force on epithelial cells in contexts where PG-mediated, aligned collagen fibrous tissue abounds, with implications for breast cancer development attributable to high MD. Finally, we summarise means through which this positive feedback mechanism of PG synthesis may be intercepted to reduce mechanical force within tissues and thus reduce disease burden.

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“…This fibre-reinforced tissue behaves in a poroelastic manner, which is driven by the collagen network resisting the swelling of the PG and associated water and thus leads to a pre-strained state in the fibrils [8] , [9] , [10] . Recently, application of X-ray and nonlinear microscopy studies have begun to shed light on the mechanics of the fibrillar network in cartilage [11] , [12] , [13] , [14] . The active role played by fibrils in response to tissue loading was demonstrated [12] through recoverable changes in fibrillar strain as measured via the axial periodicity (D-period∼65–67 nm) in collagen fibril density under stress relaxation.…”

Section: Introductionmentioning

confidence: 99%

“…When considering the mechanics of the fibrillar network in AC, the case of physiological cyclic loading in AC and the fibrillar response therein is less understood, though a few experimental studies have now revealed the fibrillar-level mechanisms in AC in response to static load or compositional changes [ [11] , [12] , [13] , 40 , 41 ]. While poroelastic modelling of cartilage mechanics [ 8 , 42 , 43 ] have advanced to include the fibrillar component [ 44 , 45 ], direct experimental visualisation of fibril-level dynamics is missing.…”

Section: Introductionmentioning

confidence: 99%

Reversible changes in the 3D collagen fibril architecture during cyclic loading of healthy and degraded cartilage

et al. 2021

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Biomechanical changes to the collagen fibrillar architecture in articular cartilage are believed to play a crucial role in enabling normal joint function. However, experimentally there is little quantitative knowledge about the structural response of the Type II collagen fibrils in cartilage to cyclic loading in situ , and the mechanisms that drive the ability of cartilage to withstand long-term repetitive loading. Here we utilize synchrotron small-angle X-ray scattering (SAXS) combined with in-situ cyclic loading of bovine articular cartilage explants to measure the fibrillar response in deep zone articular cartilage, in terms of orientation, fibrillar strain and inter-fibrillar variability in healthy cartilage and cartilage degraded by exposure to the pro-inflammatory cytokine IL-1β. We demonstrate that under repeated cyclic loading the fibrils reversibly change the width of the fibrillar orientation distribution whilst maintaining a largely consistent average direction of orientation. Specifically, the effect on the fibrillar network is a 3-dimensional conical orientation broadening around the normal to the joint surface, inferred by 3D reconstruction of X-ray scattering peak intensity distributions from the 2D pattern. Further, at the intrafibrillar level, this effect is coupled with reversible reduction in fibrillar pre-strain under compression, alongside increase in the variability of fibrillar pre-strain. In IL-1β degraded cartilage, the collagen rearrangement under cyclic loading is disrupted and associated with reduced tissue stiffness. These finding have implications as to how changes in local collagen nanomechanics might drive disease progression or vice versa in conditions such as osteoarthritis and provides a pathway to a mechanistic understanding of such diseases. Statement of significance Structural deterioration in biomechanically loaded musculoskeletal organs, e.g., joint osteoarthritis and back pain, are linked to breakdown and changes in their collagen-rich cartilaginous tissue matrix. A critical component enabling cartilage biomechanics is the ultrastructural collagen fibrillar network in cartilage. However, experimental probes of the dynamic structural response of cartilage collagen to biomechanical loads are limited. Here, we use X-ray scattering during cyclic loading (as during walking) on joint tissue to show that cartilage fibrils resist loading by a reversible, three-dimensional orientation broadening and disordering mechanism at the molecular level, and that inflammation reduces this functionality. Our results will help understand how changes to small-scale tissue mechanisms are linked to ageing and osteoarthritic progression, and development of biomaterials for joint replacements.

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Quantifying collagen fibre architecture in articular cartilage using small-angle X-ray scattering

Cited by 11 publications

References 44 publications

Proteoglycan degradation mimics static compression by altering the natural gradients in fibrillar organisation in cartilage

Proteoglycan degradation mimics static compression by altering the natural gradients in fibrillar organisation in cartilage

Mechanical Pressure Driving Proteoglycan Expression in Mammographic Density: a Self-perpetuating Cycle?

Reversible changes in the 3D collagen fibril architecture during cyclic loading of healthy and degraded cartilage

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