Multi-lipid synergy in synovial lubrication: natural redundancy vs. natural selection

The very low sliding friction of articular cartilage in the major synovial joints such as hips and knees is crucial for their well-being, and has been attributed to lubrication by phospholipid boundary layers. While single-component lipid layers have demonstrated efficient lubricity in model studies, in living joints there is a large number of different lipids, raising the question of whether this is natural redundancy, or whether this multiplicity confers any benefits. Here we examine lubrication by progressively more complex mixtures of lipids representative of those in joints, using a surface forces balance at physiologically-relevant salt concentrations and pressures. We find that different lipid combinations differ very significantly in their lubricating ability, as manifested by their robustness to hemifusion under physiological loads, pointing to a clear lubrication synergy arising from multiple lipid types in the lubricating layers. Insight into the origins of this synergy is provided by molecular dynamics (MD) simulations of the different lipid mixtures used in the experiments, which directly reveal how hemifusion - associated with greatly increased friction - depends on the detailed lipid composition. Our results provide insight into the role of lipid type proliferation in healthy synovial joints, and point to new treatment modalities for osteoarthritis

Topologically-forced electro-modulation of friction

Controlling the friction between sliding surfaces via their electric potential (electro-modulation) is a long-standing tribological goal. Phospholipid assemblies, whether as continuous bilayers or as close-packed vesicles (liposomes), form highly-lubricious surface boundary layers in aqueous media, via the hydration lubrication mechanism at the lipid-lipid interfaces, with friction coefficients {\mu}(= [force to slide]/load) down to 10-4, thus offering scope for large friction changes. Here we show that the friction between two such lipid-coated surfaces can be massively modulated through very small potentials applied to one of them, changing reversibly by up to 200-fold or more. Atomistic simulations indicate that this arises from (fully reversible) electroporation of the lipid bilayers under the potential-driven inter-surface electric fields. The porated topology of the bilayers leads to increased dehydration-induced attraction between the headgroups of opposing bilayers; at the same time, the porated bilayer structures may bridge the gap between the sliding surfaces. These effects act in parallel to modulate the friction by topologically-forcing the slip plane to pass through the intra-bilayer acyl tail interface, for which {\mu}{\approx}0.1. This enables facile, fully-reversible electro-modulation of the friction, with a dynamic range up to some 2 orders of magnitude larger than achieved to date.Comment: Yu Zhang and Di Jin contributes equally to this wor

Long-ranged attraction between disordered heterogeneous surfaces

Long-ranged attractions across water between two surfaces that are randomly covered with (mobile) positive and negative charge domains have been attributed to induced correlation of the charges (positive lining up with negative) as the surfaces approach. Here we show, by directly measuring normal forces under a rapid shear field, that these attractions may not in fact be due to such correlations. It is rather the inherent interaction-asymmetry between equally- and between oppositely-charged domains that results in the long-ranged attraction even in the complete absence of any charge correlation

Effect of Cholesterol on the Stability and Lubrication Efficiency of Phosphatidylcholine Surface Layers

The lubrication properties of saturated PC lipid vesicles containing high cholesterol content under high loads were examined by detailed surface force balance measurements of normal and shear forces between two surface-attached lipid layers. Forces between two opposing mica surfaces bearing distearoylphosphatidylcholine (PC) (DSPC) small unilamellar vesicles (SUVs, or liposomes), or bilayers, with varying cholesterol content were measured across water, whereas dimyristoyl PC (DMPC), dipalmitoyl PC (DPPC), and DSPC SUVs containing 40% cholesterol were measured across liposome dispersions of SUVs of the same lipid composition as in the adsorbed layers. The results clearly demonstrate decreased stability and resistance to normal load with the increase in cholesterol content of DSPC SUVs. Friction coefficients between two 10% cholesterol PC-bilayers were in the same range as for 40% cholesterol bilayers (μ ≈ 10-3), indicating that cholesterol has a more substantial effect on the mechanical properties of a bilayer than on its lubrication performance. We further find that the lubrication efficiency of DMPC and DPPC with 40% cholesterol is superior to that of DSPC 40% cholesterol, most likely because of enhanced hydration-lubrication in these systems. We previously found that when experiments are performed in the presence of a lipid reservoir, layers can self-heal and therefore their robustness is less important under such conditions. We conclude that the effect of cholesterol in decreasing the stability is more pronounced than its effect on hydration, but the stability is, in turn, less important when a lipid reservoir is present. This study complements our previous work and sheds light on the effect of cholesterol, a prominent and important physiological lipid, on the mechanical and lubrication properties of gel-phase lipid layers

Neutral polyphosphocholine-modified liposomes as boundary superlubricants

Boundary lubrication is associated with two sliding molecularly thin lubricated film-coated surfaces, where the energy dissipation occurs at the slip-plane between lubricated films. The hydration lubrication paradigm, which accounts for ultralow friction in aqueous media, has been extended to various systems, with phosphatidylcholine (PC) lipids recognized as extremely efficient lubrication elements due to their high hydration level. In this work, we extend a previous study (Lin et al., Langmuir 35 (2019) 6048-6054), where a charged lipid-poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) conjugate was prepared, to the very different case of a neutral lipid-PMPC) conjugate. This neutral molecule stabilizes the liposomes by attaching highly water-soluble PMPC to the surface of liposomes with its lipid moieties incorporated in the lipid bilayers. Such neutral polyphosphocholinated liposomes provide a surface lubricity which is well within the superlubrication regime (coefficient of friction = ca. 10-3 or even lower). In contrast, negatively charged lipid/polyphosphocholine conjugates modified liposomes were unable to adsorb on negatively-charged (mica) surfaces. Our method provides stable liposomes that can adsorb on negatively charged surfaces and provide superlubricity.Comment: https://authors.elsevier.com/sd/article/S0927-7757(22)00973-

A OTRIBOLOGICAL I VESTIGATIO OF THE ROLE OF PROTEOGLYCA S I BIOLUBRICATIO

ABSTRACT Articular joints in human body are uniquely efficient lubrication systems. While the cartilage surfaces slide past each other under physiological working conditions (pressure of tens of atmospheres and shear rates up to 10 6 -10 7 Hz), the friction coefficient (µ) achieves extremely low values (down to 0.001) never successfully reached by mechanical prosthetic devices. Friction studies on polymer brushes attached to surfaces have recently demonstrated (17) their ability to reduce friction between the rubbing surfaces to extremely low values by means of the hydrated ions and the charges on the polymer chains. We propose that the extremely efficient lubrication observed in living joints arises from the presence of a brush-like phase of charged macromolecules at the surface of the cartilage superficial zone: hydration layers which surround the charges on the cartilage macromolecules might provide a lubricating ball-bearing-like effect as demonstrated for the synthetic polyelectrolytes (17). In this work macromolecules of the cartilage superficial zone (aggrecans) are extracted from human femoral heads and purified using well developed biochemical techniques (20). The extracted molecules are then characterized with atomic force microscope (AFM). By means of a surface force balance (SFB) normal and shear interactions between mica surfaces coated with these molecules are examined focusing on the frictional forces between such surfaces at normal stresses similar to those in human joints

The Role of Hyaluronic Acid in Cartilage Boundary Lubrication

Hydration lubrication has emerged as a new paradigm for lubrication in aqueous and biological media, accounting especially for the extremely low friction (friction coefficients down to 0.001) of articular cartilage lubrication in joints. Among the ensemble of molecules acting in the joint, phosphatidylcholine (PC) lipids have been proposed as the key molecules forming, in a complex with other molecules including hyaluronic acid (HA), a robust layer on the outer surface of the cartilage. HA, ubiquitous in synovial joints, is not in itself a good boundary lubricant, but binds the PC lipids at the cartilage surface; these, in turn, massively reduce the friction via hydration lubrication at their exposed, highly hydrated phosphocholine headgroups. An important unresolved issue in this scenario is why the free HA molecules in the synovial fluid do not suppress the lubricity by adsorbing simultaneously to the opposing lipid layers, i.e., forming an adhesive, dissipative bridge between them, as they slide past each other during joint articulation. To address this question, we directly examined the friction between two hydrogenated soy PC (HSPC) lipid layers (in the form of liposomes) immersed in HA solution or two palmitoyl–oleoyl PC (POPC) lipid layers across HA–POPC solution using a surface force balance (SFB). The results show, clearly and surprisingly, that HA addition does not affect the outstanding lubrication provided by the PC lipid layers. A possible mechanism indicated by our data that may account for this is that multiple lipid layers form on each cartilage surface, so that the slip plane may move from the midplane between the opposing surfaces, which is bridged by the HA, to an HA-free interface within a multilayer, where hydration lubrication is freely active. Another possibility suggested by our model experiments is that lipids in synovial fluid may complex with HA, thereby inhibiting the HA molecules from adhering to the lipids on the cartilage surfaces

Normal and shear forces between a polyelectrolyte brush and a solid surface

The diblock copolymer poly(methyl methacrylate)-b-poly(sodium sulfonated glycidyl methacrylate) (PMMA-b-PSGMA) was end-attached by its hydrophobic block (PMMA) onto mica hydrophobized by a stearic trimethylammonium iodide (STAI) layer, to form a polyelectrolyte brush immersed in water. With a surface force balance (SFB), we extended earlier measurements between two such brush layers for the case of normal and shear forces at different shear rates, surface separation, and compressions between one mica surface coated with STAI or a STAI-diblock layer against a bare mica surface. After coating one of the surfaces with STAI, a long range attraction that results in a jump into an adhesive flat contact between the hydrophobic and hydrophilic surfaces was observed. A very different behavior was seen after forming the polyelectrolyte brush on the STAI-coated surface. The long range attraction was replaced by repulsion, accompanied by very low friction during shear (ca. three orders of magnitude lower than with adsorbed polyelectrolytes). On further compression, a weak attraction to the adhesive contact was observed. From the final surface-surface contact separation, we deduce that most of the polyelectrolyte diblock brush layer was squeezed out from the gap, leaving the STAI layer and a small amount of the polymer attached to the surface. Stick-sliding behavior was seen while applying shear, suggesting a dissipation mechanism caused by the trapped polyelectrolyte