Ronit Goldberg

Boundary lubricants with exceptionally low friction coefficients based on 2D close-packed phosphatidylcholine liposomes.

Figure 1 . Cryo-SEM image of the HSPC-SUV adsorbed on freshly cleaved mica. The lower inset schematically interprets this in terms of liposomes that have fl attened (A), those with less available space for fl attening (B) and those (C) on top of the close-packed surface-attached layer that were not removed by the washing. The top right inset shows an AFM profi le of the same close-packed layer; holes in the originally close-packed layer arise through removal of liposomes by the AFM tip. Liposomes are widely used in pharmaceutical applications, primarily as drug delivery vehicles, as well as in gene therapy and for diagnostic imaging. [ 1–3 ] Here we report that certain phosphatidylcholine liposomes, when adsorbed onto sliding surfaces in a 2-dimensional close-packed array, may act as exceptionally effi cient boundary lubricants at physiologically high pressures [ 4 ] under water. We created small unilamellar vesicles (SUVs) of hydrogenated soy phosphatidylcholine (HSPC) lipids which self-assemble in close-packed layers on solid surfaces to reduce the coeffi cient μ of sliding friction between them down to values μ ≈ 10 − 4 –2 × 10 − 5 , at pressures up to at least ca. 12 MPa (ca. 120 atmospheres). Such low values of the friction at these high pressures have not been attained with any boundary lubricants. This remarkably low friction is attributed to lubrication by the highly-hydrated phosphocholine head-groups exposed at the vesicle walls, stabilized against high pressures by the closepacking and by the rigidity of the gel-phase liposomes. A dispersion of HSPC-SUV with a unimodal size distribution (diameter 65 nm) was prepared as described below (Experimental); freshly cleaved mica surfaces were incubated in the dispersion, then rinsed and mounted in a surface force balance [ 5 ] (SFB) under water.

Supramolecular synergy in the boundary lubrication of synovial joints.

Hyaluronan, lubricin and phospholipids, molecules ubiquitous in synovial joints, such as hips and knees, have separately been invoked as the lubricants responsible for the remarkable lubrication of articular cartilage; but alone, these molecules cannot explain the extremely low friction at the high pressures of such joints. We find that surface-anchored hyaluronan molecules complex synergistically with phosphatidylcholine lipids present in joints to form a boundary lubricating layer, which, with coefficient of friction μ≈0.001 at pressures to over 100 atm, has a frictional behaviour resembling that of articular cartilage in the major joints. Our findings point to a scenario where each of the molecules has a different role but must act together with the others: hyaluronan, anchored at the outer surface of articular cartilage by lubricin molecules, complexes with joint phosphatidylcholines to provide the extreme lubrication of synovial joints via the hydration–lubrication mechanism.

Interactions between Adsorbed Hydrogenated Soy Phosphatidylcholine (HSPC) Vesicles at Physiologically High Pressures and Salt Concentrations

Using a surface force balance, we measured normal and shear interactions as a function of surface separation between layers of hydrogenated soy phosphatidylcholine (HSPC) small unilamellar vesicles (SUVs) adsorbed from dispersion at physiologically high salt concentrations (0.15 M NaNO₃). Cryo-scanning electron microscopy shows that each surface is coated by a close-packed HSPC-SUV layer with an overlayer of liposomes on top. A clear attractive interaction between the liposome layers is seen upon approach and separation, followed by a steric repulsion upon further compression. The shear forces reveal low friction coefficients (μ = 0.008-0.0006) up to contact pressures of at least 6 MPa, comparable to those observed in the major joints. The spread in μ-values may be qualitatively accounted for by different local liposome structure at different contact points, suggesting that the intrinsic friction of the HSPC-SUV layers at this salt concentration is closer to the lower limit (μ = ~0.0006). This low friction is attributed to the hydration lubrication mechanism arising from rubbing of the hydrated phosphocholine-headgroup layers exposed at the outer surface of each liposome, and provides support for the conjecture that phospholipids may play a significant role in biological lubrication.

Hydration lubrication: exploring a new paradigm

Lubrication by hydration shells that surround, and are firmly attached to, charges in water, and yet are highly fluid, provide a new mode for the extreme reduction of friction in aqueous media. We report new measurements, using a mica surface-force balance, on several different systems which exhibit hydration lubrication, extending earlier studies significantly to shed new light on the nature and limits of this mechanism. These include lubrication by hydrated ions trapped between charged surfaces, and boundary lubrication by surfactants, by polyzwitterionic brushes and by close-packed layers of phosphatidylcholine vesicles. Sliding friction coefficients as low as 10(-4) or even lower, and mean contact pressures of up to 17 MPa or higher are indicated. This suggests that the hydration lubrication mechanism may underlie low-friction sliding in biological systems, in which such pressures are rarely exceeded.

Liposomes as lubricants: beyond drug delivery.

In this paper we review recent work (Goldberg et al., 2011a,b) on a new use for phosphatidylcholine liposomes: as ultra-efficient boundary lubricants at up to the highest physiological pressures. Using a surface force balance, we have measured the normal and shear interactions as a function of surface separation between layers of hydrogenated soy phophatidylcholine (HSPC) small unilamellar vesicles (SUVs) adsorbed from dispersion, at both pure water and physiologically high salt concentrations of 0.15 M NaNO(3). Cryo-Scanning Electron Microscopy shows each surface to be coated by a close-packed HSPC-SUV layer with an over-layer of liposomes on top. The shear forces reveal strikingly low friction coefficients down to 2×10(-5) in pure water system or 6×10(-4) in the 150 mM salt system, up to contact pressures of at least 12 MPa (pure water) or 6 MPa (high salt), comparable with those in the major joints. This low friction is attributed to the hydration lubrication mechanism arising from rubbing of the highly hydrated phosphocholine-headgroup layers exposed at the outer surface of each liposome, and provides support for the conjecture that phospholipids may play a significant role in biological lubrication.

Effect of Glucosamine Sulfate on Surface Interactions and Lubrication by Hydrogenated Soy Phosphatidylcholine (HSPC) Liposomes

Glucosamine sulfate (GAS) is a charged monosaccharide molecule that is widely used as a treatment for osteoarthritis, a joint disease related to friction and lubrication of articular cartilage. Using a surface force balance, we examine the effect of GAS on normal and, particularly, on shear (frictional) interactions between surfaces in an aqueous environment coated with small unilamellar vesicles (SUVs), or liposomes, of hydrogenated soy phosphatidylcholine (HSPC). We examine the effect of GAS solution, pure water, and salt solution (0.15 M NaNO3) both inside and outside the vesicles. Cryoscanning electron microscopy shows a closely packed layer of liposomes whose morphology is affected only slightly by GAS. HSPC-SUVs with encapsulated GAS are stable upon shear at high compressions (>100 atm) and provide very good lubrication when immersed both in pure water and physiological-level salt solutions (in the latter case, the liposomes are exceptionally stable and lubricious up to >400 atm). The low friction is attributed to several parameters based on the hydration lubrication mechanism.