Nanomechanics of opposing glycosaminoglycan macromolecules

Seog, Joonil; Dean, Delphine; Rolauffs, Bernd; Wu, Tao; Genzer, Jan; Plaas, Anna; Grodzinsky, Alan J.; Ortiz, Christine

doi:10.1016/j.jbiomech.2004.09.010

Cited by 40 publications

(36 citation statements)

References 31 publications

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“…1-3). Our measurements of bovine AC stiffness were similar to those previously reported in healthy human cartilage (Seog et al, 2005;Treppo et al, 2000) and, consequently, the fragmentation, which was observed, did not adversely affect the compressive modulus. Therefore, contrary to previous models (Eisenberg and Grodzinsky, 1985;Seog et al, 2005), mechanically competent tissues could be comprised of fragmented, non-HA (hyaluronic acid)-associated aggrecan (Fig.…”

Section: Discussionsupporting

confidence: 91%

“…Protease-driven fragmentation of aggrecan is likely to influence tissue function. Aggrecan structure mediates single molecule mechanics and GAG-GAG interactions account for 30-50 % of the compressive modulus in the AC (Eisenberg and Grodzinsky, 1985;Seog et al, 2005). However, these models assume that aggrecan structure is homogeneous (with regards to core-protein length and GAG sulphation) rather than, as demonstrated in this study, heterogeneous (both within and between tissues) (Fig.…”

Section: Discussionmentioning

confidence: 73%

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Extracellular matrix fragmentation in young, healthy cartilaginous tissues

Craddock

Hodson²,

Ozols

et al. 2018

eCM

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Although the composition and structure of cartilaginous tissues is complex, collagen II fibrils and aggrecan are the most abundant assemblies in both articular cartilage (AC) and the nucleus pulposus (NP) of the intervertebral disc (IVD). Whilst structural heterogeneity of intact aggrecan ( containing three globular domains) is well characterised, the extent of aggrecan fragmentation in healthy tissues is poorly defined. Using young, yet skeletally mature (18-30 months), bovine AC and NP tissues, it was shown that, whilst the ultrastructure of intact aggrecan was tissue-dependent, most molecules (AC: 95 %; NP: 99.5 %) were fragmented (lacking one or more globular domains). Fragments were significantly smaller and more structurally heterogeneous in the NP compared with the AC (molecular area; AC: 8543 nm 2 ; NP: 4625 nm 2 ; p < 0.0001). In contrast, fibrillar collagen appeared structurally intact and tissue-invariant. Molecular fragmentation is considered indicative of a pathology; however, these young, skeletally mature tissues were histologically and mechanically (reduced modulus: AC: ≈ 500 kPa; NP: ≈ 80 kPa) comparable to healthy tissues and devoid of notable gelatinase activity (compared with rat dermis). As aggrecan fragmentation was prevalent in neonatal bovine AC (99.5 % fragmented, molecular area: 5137 nm 2 ) as compared with mature AC (95.0 % fragmented, molecular area: 8667nm 2 ), it was hypothesised that targeted proteolysis might be an adaptive process that modified aggrecan packing (as simulated computationally) and, hence, tissue charge density, mechanical properties and porosity. These observations provided a baseline against which pathological and/or age-related fragmentation of aggrecan could be assessed and suggested that new strategies might be required to engineer constructs that mimic the mechanical properties of native cartilaginous tissues.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 73%

Extracellular matrix fragmentation in young, healthy cartilaginous tissues

Craddock

Hodson²,

Ozols

et al. 2018

eCM

View full text Add to dashboard Cite

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“…This is consistent with the observation that κ -1 (0.01 M) ∼ 3 nm is on the order of the inter-GAG chain spacing along the aggrecan core protein. In contrast, the height of a sparsely populated CS-GAG brush (measured by ellipsometry) 2 was found previously to decrease from pH ) 5 to 3 at 0.01 M IS. However, the GAG-GAG spacing in that system (6.5 nm) was ∼3-4 times greater than that within the aggrecan brush used here.…”

mentioning

confidence: 49%

Nanoscale Conformation and Compressibility of Cartilage Aggrecan Using Microcontact Printing and Atomic Force Microscopy

et al. 2005

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“…The large number of localized GAGs and their high electronegativity allows them to trap large amounts of water. They are found in large quantities in highly hydrated tissues like articular cartilage that experience primarily hydrostatic loading conditions (Basalo et al, 2004;Frank et al, 1987;Seog et al, 2005;Theocharis et al, 2001;Zhu et al, 1993). The presence of versican and aggrecan in ligament may suggest similar physiological roles.…”

Section: Discussionmentioning

confidence: 99%

Spatial distribution and orientation of dermatan sulfate in human medial collateral ligament

Henninger

Maas

Underwood

et al. 2007

Journal of Structural Biology

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The proteoglycan decorin and its associated glycosaminoglycan (GAG), dermatan sulfate (DS), regulate collagen fibril formation, control fibril diameter and have been suggested to contribute to the mechanical stability and material properties of connective tissues. The spatial distribution and orientation of DS within the tissue are relevant to these mechanical roles, but measurements of length and orientation from 2D transmission electron microscopy (TEM) are prone to errors from projection. The objectives of this study were to construct a 3D geometric model of DS GAGs and collagen fibrils, and to use the model to interpret TEM measurements of the spatial orientation and length of DS GAGs in the medial collateral ligament of the human knee. DS was distinguished from other sulfated GAGs by treating tissue with chondroitinase B, an enzyme that selectively degrades DS. An image processing pipeline was developed to analyze the TEM micrographs. The 3D model of collagen and GAGs quantified the projection error in the 2D TEM measurements. Model predictions of 3D GAG orientation were highly sensitive to the assumed GAG length distribution, with the baseline input distribution of 69 ± 23 nm providing the best predictions of the angle measurements from TEM micrographs. The corresponding orientation distribution for DS GAGs was maximal at orientations orthogonal to the collagen fibrils, tapering to near zero with axial alignment. Sulfated GAGs that remained after chondroitinase B treatment were preferentially aligned along the collagen fibril. DS therefore appears more likely to bridge the interfibrillar gap than non-DS GAGs. In addition to providing quantitative data for DS GAG length and orientation in the human MCL, this study demonstrates how a 3D geometric model can be used to provide a priori information for interpretation of geometric measurements from 2D micrographs.

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Nanomechanics of opposing glycosaminoglycan macromolecules

Cited by 40 publications

References 31 publications

Extracellular matrix fragmentation in young, healthy cartilaginous tissues

Extracellular matrix fragmentation in young, healthy cartilaginous tissues

Nanoscale Conformation and Compressibility of Cartilage Aggrecan Using Microcontact Printing and Atomic Force Microscopy

Spatial distribution and orientation of dermatan sulfate in human medial collateral ligament

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