Liposomes Act as Effective Biolubricants for Friction Reduction in Human Synovial Joints

Abstract

Phospholipids (PL) form the matrix of biological membranes and of the lipoprotein envelope monolayer, and are responsible for many of the unique physicochemical, biochemical, and biological properties of these supermolecular bioassemblies. It was suggested that phospholipids present in the synovial fluid (SF) and on the surface of articular cartilage have major involvement in the low friction of cartilage, which is essential for proper mobility of synovial joints. In pathologies, such as impaired biolubrication (leading to common joint disorders such as osteoarthritis), the level of phospholipids in the SF is reduced. Using a human-sourced cartilage-on-cartilage setup, we studied to what extent and how phospholipids act as highly effective cartilage biolubricants. We found that large multilamellar vesicles (MLV), >800 nm in diameter, composed of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) or of a mixture of DMPC and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) are superior lubricants in comparison to MLV composed of other phosphatidylcholines. Introducing cholesterol into liposomes resulted in less effective lubricants. DMPC-MLV was also superior to small unilamellar vesicles (SUV), <100 nm in diameter, composed of DMPC. MLV are superior to SUV due to MLV retention at and near (<200 microm below) the cartilage surface, while SUV penetrate deeper into the cartilage (450-730 microm). Superiority of specific PL compositions is explained by the thermotropic behavior (including compressibility) of the lipid bilayer. Correlating physicochemical properties of the MLV with the friction results suggests that MLV having lipid bilayers in the liquid-disordered phase and having a solid-ordered to liquid-disordered phase transition temperature slightly below physiological temperature are optimal for lubrication. High phospholipid headgroup hydration, high compressibility, and softness are the common denominators of all efficient PL compositions. The high efficiency of DMPC-MLV and DMPC/DPPC-MLV as cartilage lubricants combined with their resistance to degradation at 37 degrees C supports further evaluation of these MLV for treatment of joint impairments related to poor lubrication. This work also demonstrates the relevance of basic physicochemical properties of phospholipids to their activities in biological systems.

Boundary Lubricants with Exceptionally Low Friction Coefficients Based on 2D Close‐Packed Phosphatidylcholine Liposomes

“…When the highly-hydrated outer phosphocholine layers are screened by using poly(ethylene glycol)(PEG)-coated-HSPC-SUV [ 1 ] layers as the boundary layers, the friction is very much higher than with the pure HSPC component: This is consistent biological tissues. [ 8 , 9 ] Earlier work [ 10 ] has examined liposome layers using a friction-force microscope (though the sharp tip with radius smaller than the liposomes may lead to ploughing effects), and liposomes added to soft (cartilage) surfaces using a tribometer, [ 11 ] as well as lipid bilayers. [12 , 13 ] Recently friction coeffi cients down to 4 × 10 − 4 at pressures up to 7.5 MPa were observed between covalently grafted polyzwitterionic brushes.…”

Phospholipid Vesicles in Media for Tribological Studies against Live Cartilage

“…It has been proposed that together with HA this forms a gel-like structure with proteins in the synovial fluid, and the lipid multilayer provides the fluid with better lubricating properties, helping to reduce friction within the joint [23]. Recently, using atomic force microscopy (AFM), Raj et al [24] determined that hyaluronic acid and phospholipid vesicles adsorbed onto silica act synergistically to produce multilayer structures that yield a very low friction coefficient (<0.01).…”

The Probable Explanation for the Low Friction of Natural Joints

“…6), and secondly, through hydration repulsion and adhesion SF macromolecules on the PL membrane [16,53]. Charged lamellar aggregates, liposomes and macromolecules act electrostatically on negatively charged cartilage surfaces [13,19,30,44,[49][50][51].…”