Viscoelastic Properties of Hyaluronan in Physiological Conditions

Abstract

Hyaluronan (HA) is a high molecular weight glycosaminoglycan of the extracellular matrix (ECM), which is particularly abundant in soft connective tissues. Solutions of HA can be highly viscous with non-Newtonian flow properties. These properties affect the movement of HA-containing fluid layers within and underlying the deep fascia. Changes in the concentration, molecular weight, or even covalent modification of HA in inflammatory conditions, as well as changes in binding interactions with other macromolecules, can have dramatic effects on the sliding movement of fascia. The high molecular weight and the semi-flexible chain of HA are key factors leading to the high viscosity of dilute solutions, and real HA solutions show additional nonideality and greatly increased viscosity due to mutual macromolecular crowding. The shear rate dependence of the viscosity, and the viscoelasticity of HA solutions, depend on the relaxation time of the molecule, which in turn depends on the HA concentration and molecular weight. Temperature can also have an effect on these properties. High viscosity can additionally affect the lubricating function of HA solutions. Immobility can increase the concentration of HA, increase the viscosity, and reduce lubrication and gliding of the layers of connective tissue and muscle. Over time, these changes can alter both muscle structure and function. Inflammation can further increase the viscosity of HA-containing fluids if the HA is modified via covalent attachment of heavy chains derived from Inter-α-Inhibitor. Hyaluronidase hydrolyzes HA, thus reducing its molecular weight, lowering the viscosity of the extracellular matrix fluid and making outflow easier. It can also disrupt any aggregates or gel-like structures that result from HA being modified. Hyaluronidase is used medically primarily as a dispersion agent, but may also be useful in conditions where altered viscosity of the fascia is desired, such as in the treatment of muscle stiffness.

Useful In Vitro Techniques to Evaluate the Mucoadhesive Properties of Hyaluronic Acid-Based Ocular Delivery Systems

“…The elastic energy is stored and the viscous dissipates, which is the reason at high frequencies the G′ moduli is higher than G″. Other explanation given by Cowman et al [33] justifies the crossover due to the HA molecules relaxation time. When a solution is cyclically deformed, at slow rates the molecules are capable of keeping up with changes and behave in a viscous form.…”

Tissue mechanics regulate brain development, homeostasis and disease

“…1). The viscoelastic nature of the brain contributes to its unique mechanical properties, and different ECM compartments of the brain (Cowman et al, 2015), neuronal cell types and even intercellular compartments could vary greatly in viscoelastic parameters (Lu et al, 2006). Because these differences are just beginning to be understood, and often in the context of repair after traumatic injury (MacManus et al, 2016;Li et al, 2016;Johnson et al, 2016), we do not address viscoelastic properties in great detail in this review.…”

Knockout of hyaluronan synthase 1, but not 3, impairs formation of the retrocalcaneal bursa

“…At the molecular level, a metastable homeostatic interaction between HA and H 2 O molecules can form to promote tissue hydration and surface lubrication (1–3). From a biophysical perspective, the size, hydration, and hydrodynamic shape of HA polymers provide for high viscosity and increased relaxation time, thereby conferring viscoelasticity during physical deformation (4). …”