Department of Biomedical Engineering, Technion-Israel Institute of Technology, Haifa 32000, Israel.
Langmuir. 2010 Jan 19;26(2):1107-16. doi: 10.1021/la9024712.
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.
磷脂（PL）构成生物膜和脂蛋白包膜单层的基质，并负责这些超分子生物组装体的许多独特的物理化学、生化和生物学特性。有人提出，滑液（SF）和关节软骨表面存在的磷脂对软骨的低摩擦有主要影响，这对滑膜关节的正常运动至关重要。在病理情况下，如生物润滑不良（导致常见的关节疾病，如骨关节炎），SF 中的磷脂水平降低。使用源自人类的软骨对软骨设置，我们研究了磷脂在多大程度上以及如何作为高效的软骨生物润滑剂发挥作用。我们发现，由 1,2-二肉豆蔻酰-sn-甘油-3-磷酸胆碱（DMPC）或 DMPC 和 1,2-二月桂酰基-sn-甘油-3-磷酸胆碱（DPPC）组成的直径大于 800nm 的大多层囊泡（MLV）比由其他磷脂组成的 MLV 具有更好的润滑性能。向脂质体中引入胆固醇会导致润滑效果降低。DMPC-MLV 也优于直径小于 100nm 的由 DMPC 组成的小单层囊泡（SUV）。MLV 优于 SUV，因为 MLV 保留在软骨表面及其附近（低于软骨表面 200μm 以内），而 SUV 则更深地渗透到软骨中（450-730μm）。特定 PL 成分的优越性是由脂质双层的热致行为（包括压缩性）解释的。将 MLV 的物理化学性质与摩擦结果相关联表明，具有液态无序相脂质双层且具有略低于生理温度的固态有序到液态无序相变温度的 MLV 是最佳的润滑选择。高磷脂头部基团水合作用、高压缩性和柔软性是所有高效 PL 成分的共同特征。DMPC-MLV 和 DMPC/DPPC-MLV 作为软骨润滑剂的高效率及其在 37°C 下抗降解的能力支持进一步评估这些 MLV 用于治疗与润滑不良相关的关节损伤。这项工作还证明了磷脂基本物理化学性质与其在生物系统中的活性之间的相关性。
