Rheological Properties of Cartilage Glycosaminoglycans and Proteoglycans

Abstract

Glycosaminoglycans (GAGs) are molecules that govern the load-bearing and frictional properties of cartilage and the lubricating properties of synovial fluid of joints. Most GAGs in the body form proteoglycans (PGs), and the dominant PG in cartilage is the bottlebrush-shaped aggrecan, comprised of a protein core decorated by GAG side chains consisting mainly of chondroitin sulfate (CS) and keratan sulfate. Additionally, hyaluronic acid (HA) induces aggrecan to self-assemble into complexes having up to 100 aggrecan molecules attached to each HA chain “backbone”. Here, we report the rheological properties of CS, HA, aggrecan, and aggrecan–HA complexes in water and salt solutions. We find that CS solutions are viscous liquids, while HA solutions exhibit viscoelasticity and shear thinning. Specifically, in the case of HA, the storage modulus G′ exceeds the loss modulus G″ at high frequencies (ω) while the reverse is true at low ω. Thus, the rheologies of CS and HA exhibit somewhat distinct viscoelastic properties. Aggrecan, on the other hand, shows a rheology consistent with an incipient “weak gel” in which G′ and G″ cross at a specific ω and follow a power-law scaling over a wide ω range. Moreover, aggrecan samples do not attain an observable plateau in the viscosity under steady shear and low shear rates. Finally, the complexation of aggrecan and HA over a period of 48 h results in a slow evolution (“aging”) in measured rheological properties, with G′ at low ω progressively increases in time, while G″ remains essentially unchanged. This suggests that aggrecan and HA gradually form a macroscopic network in which molecular complexes act as physical cross-links.

Cartilage-Inspired Hydrogel with Mechanical Adaptability, Controllable Lubrication, and Inflammation Regulation Abilities

“…In general, the excellent load-bearing/shear-resistance/lubrication capacities of cartilage are associated with the aligning extracellular matrix (ECM), consisting of collagen II, proteoglycan, and lubricin. − Proteoglycan, consisting of hyaluronic acid (HA) and aggrecan (including chondroitin sulfate, keratan sulfate, and haptoglobin), is rich in carboxylate and sulfonate groups and interpenetrates the superficial zone of the cartilage. , Moreover, HA is also an effective natural polysaccharide for inflammation management . Another key biomacromolecule for joint lubrication is lubricin with sulfonate groups, the secretion of which could be enhanced by normal sliding motion .…”

Cartilage polymers: From viscoelastic solutions to weak gels*

“…Rheological experiments were conducted on an AR2000 stress-controlled rheometer (TA Instruments). [45] Experiments were done on a cone-and-plate geometry (40 mm diameter, 2 cone angle), and a solvent trap was used to prevent evaporation of the sample during the tests. The temperature was controlled by a Peltier assembly on the rheometer, and all experiments were made at 25 C. Dynamic frequency sweep experiments were conducted in the linear viscoelastic regime for each sample, which was first determined from strain-sweep experiments.…”

Sericin nano-gel agglomerates mimicking the pericellular matrix induce the condensation of mesenchymal stem cells and trigger cartilage micro-tissue formation without exogenous stimulation of growth factorsin vitro

“…The expression and distribution of proteoglycans (aggrecan, a typical component of cartilaginous extracellular matrix) 44 were Fig. 2 (a) Proliferation of MSCs cultured with various types of media.…”

“…More MSC micro-masses were formed in 0.1% sericin nano-gel group that corresponded to the result that more abundance of aggrecan was expressed by the 0.1% sericin nano-gel group. GAGs (glycosaminoglycans), which represent the functional unit of the cartilage tissue, 44 were visualized by safranin O-staining, as shown in Fig. 5(a) (safranine O) and Fig.…”