title: 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.
authors.affiliation: Department of Biomedical Engineering, Technion-Israel Institute of Technology, Haifa 32000, Israel.
authors.forename: Sarit
authors.initials: S
authors.lastname: Sivan
authors.forename: Avi
authors.initials: A
authors.lastname: Schroeder
authors.forename: Gabi
authors.initials: G
authors.lastname: Verberne
authors.forename: Yulia
authors.initials: Y
authors.lastname: Merkher
authors.forename: Dvora
authors.initials: D
authors.lastname: Diminsky
authors.forename: Aba
authors.initials: A
authors.lastname: Priev
authors.forename: Alice
authors.initials: A
authors.lastname: Maroudas
authors.forename: Gregory
authors.initials: G
authors.lastname: Halperin
authors.forename: Dorrit
authors.initials: D
authors.lastname: Nitzan
authors.forename: Izhak
authors.initials: I
authors.lastname: Etsion
authors.forename: Yechezkel
authors.initials: Y
authors.lastname: Barenholz
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry / Q000494:pharmacology; D000368:Aged; D000369:Aged, 80 and over; D002356:Cartilage / Q000187:drug effects / Q000502:physiology; D004134:Dimyristoylphosphatidylcholine / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008081:Liposomes / Q000737:chemistry* / Q000494:pharmacology; D054327:Lubricants / Q000737:chemistry* / Q000494:pharmacology; D008875:Middle Aged; D008962:Models, Theoretical; D013501:Surface-Active Agents / Q000737:chemistry / Q000494:pharmacology; D013582:Synovial Fluid / Q000737:chemistry*
chemical_list: D008081:Liposomes; D054327:Lubricants; D013501:Surface-Active Agents; D015060:1,2-Dipalmitoylphosphatidylcholine; D004134:Dimyristoylphosphatidylcholine