Effects of Hyaluronan Molecular Weight on the Lubrication of Cartilage-Emulating Boundary Layers.

Zhang Liu,Jacob Klein,Yaxun Fan,Yilin Wang,Nir Kampf,Weifeng Lin

doi:10.1021/acs.biomac.0c01151

Abstract

Osteoarthritic joints contain lower-molecular-weight (MW) hyaluronan (hyaluronic acid, HA) than healthy joints. To understand the relevance of this HA size effect for joint lubrication, the friction and surface structure of cartilage-emulating surfaces with HA of different MWs were studied using a surface force balance (SFB) and atomic force microscopy (AFM). Gelatin (gel)-covered mica surfaces were coated with high-MW HA (HHA), medium-MW HA (MHA), or low-MW HA (LHA), and lipids of hydrogenated soy l-α-phosphatidylcholine (HSPC) in the form of small unilamellar vesicles, using a layer-by-layer assembly method. SFB results indicate that the gel-HHA-HSPC boundary layer provides very efficient lubrication, attributed to hydration lubrication at the phosphocholine headgroups exposed by the HA-attached lipids, with friction coefficients (COF) as low as 10–3–10–4 at contact stresses at least up to P = 120 atm. However, for the gel-MHA-HSPC and gel-LHA-HSPC surfaces, the friction, initially low, increases sharply at much lower pressures (up to 30–60 atm at most). This higher friction with the shorter chains may be due to their weaker total adhesion energy to the gelatin, where the attraction between the negatively charged HA and the weakly positively charged gelatin is attributed largely to counterion-release entropy. Thus, the complexes of LHA and MHA with the lubricating HSPC lipids are more easily removed by shear during sliding, especially at high stresses, than the HHA-HSPC complex, which is strongly adhered to gelatin. This is ultimately the reason for lower-pressure lubrication breakdown with the shorter polysaccharides. Our results provide molecular-level insight into why the decrease in HA molecular weight in osteoarthritic joints may be associated with higher friction at the articular cartilage surface, and may have relevance for treatments of osteoarthritis involving intra-articular HA injections.

Highlights

Osteoarthritic (OA) joints exhibit degraded articular cartilage, which may be associated with breakdown in lubrication, and reveal a decrease in the molecular weight (MW) of hyaluronic acid (HA), a polysaccharide ubiquitous in cartilage and in the surrounding synovial fluid.[3−5] It is of interest to examine the effect of HA MW on the lubrication of articular cartilage in synovial joints
Our results suggest that the gel-hydrogenated soy L-α-phosphatidylcholine (HSPC) lubrication breaks down when the PC vesicles are detached from the gelatin, while for gel-LHAHSPC and gel-MW HA (MHA)-HSPC, it is the detachment of the HA that results in lubrication breakdown
The relation of osteoarthritis to the length of HA in synovial joints has been debated for many years.[56]

Summary

Introduction

Healthy articular cartilage is a self-lubricating system with extremely low friction coefficients (COF), as low as 10−3 even at pressures up to 100 atm.[1,2] Compared to healthy joints, osteoarthritic (OA) joints exhibit degraded articular cartilage, which may be associated with breakdown in lubrication, and reveal a decrease in the molecular weight (MW) of hyaluronic acid (HA), a polysaccharide ubiquitous in cartilage and in the surrounding synovial fluid.[3−5] It is of interest to examine the effect of HA MW on the lubrication of articular cartilage in synovial joints.One method that has been used to overcome the shortage of HA in OA joints is its replenishment via intra-articular injection of high-MW HA (HHA), known as viscosupplementation.[6−11] In spite of the wide application of the HHA in viscosupplementation, there is still debate on whether it is significantly better than placebo.[8,10,12,13] the precise mechanistic role of HA in maintaining the health and effective lubrication of synovial joint is still not fully understood,[6,14] since HA solutions at the shear rates between cartilage surfaces in joints have viscosity close to water,[15,16] while boundary layers of HA on its own cannot provide the necessary lubrication to the healthy joints under high pressure, regardlessReceived: August 2, 2020 Revised: September 12, 2020 Published: September 15, 2020Biomacromolecules pubs.acs.org/BiomacArticle of their MW.[17−20] it has been suggested that instead of working directly as a lubricant, HA is potentially interacting with other components in the cartilage to form supramolecular boundary layers, which in turn mediate the lubrication.[21−26] The increasing friction in OA joints may be correlated with the different molecular interactions of lower-molecularweight HA with other components in the synovial joints. Single-molecule microscopy reveals that the diffusion coefficient of HA in healthy synovial fluid was on average 30% slower than expected by sample viscosity, suggesting that HA undergoes intermolecular interactions in healthy joints These interactions were diminished or missing in samples from patients with osteoarthritis.[27] Other studies suggest specific interactions of HA with other synovial joint macromolecules, some though not all of which depend on the HA MW.[18] This suggests that HAs of different MWs may interact differently with other components in synovial joints, especially the surface-active phospholipids,[28−32] which are key bio-lubricants that, in the form of boundary layers, can provide both low friction (COF 10−3−10−4) and high load-bearing capacity This suggests that HAs of different MWs may interact differently with other components in synovial joints, especially the surface-active phospholipids,[28−32] which are key bio-lubricants that, in the form of boundary layers, can provide both low friction (COF 10−3−10−4) and high load-bearing capacity (contact stresses ca. 100−150 atm) comparable to healthy cartilage.[33−39]

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