Biointerface Science: Composition-Structure-Function Relationship of Synovial Fluid's Cartilage Boundary Lubricants

生物界面科学：滑液软骨边界润滑剂的成分-结构-功能关系

• 批准号: RGPIN-2014-06518
• 负责人: Schmidt, Tannin
• 金额: $ 2.19万
• 依托单位: University of Calgary
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2016
• 资助国家: 加拿大
• 起止时间: 2016-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=612277
• 关键词: Biointerface; Science; Composition; Structure; Function

A biointerface is an interface between a cell, molecule, tissue, or biomaterial with another tissue or biomaterial. Biointerface science contributes to the understanding of interactions between molecules and surfaces; interactions of molecules, and their resulting function, at a surface can be different to those in solution. Biointerfaces are central to natural science and (bio)engineering, and crucial in research relating to many fields, including biotribology. Biotribology is the study of lubrication, friction and wear of sliding biological surfaces that provides insight into the fundamental mechanisms of biolubrication. The overall goal of my research program is to understand the fundamental and regulatory mechanisms of the biotribological and biophysical properties of proteoglycan 4 (PRG4, a critical biological boundary lubricant) at relevant biointerfaces and biomaterials. Articular cartilage is a tissue in the body that bears load and slides relative to an apposing tissue surface, thus forming a biointerface, in a fluid-filled cavity. The remarkable low-friction and low-wear properties of cartilage are facilitated by multiple modes of lubrication involving cartilage, the surrounding synovial fluid and its constituents, and their interaction. Boundary lubrication is an important and operative mode where surface-to-surface contact occurs, and molecules at the surface provide lubrication function. Two critical boundary lubricant molecules present in synovial fluid and at the surface of cartilage are PRG4 and hyaluronan (HA). Both function as dose-dependent cartilage boundary lubricants, and also act together to reduce friction to levels near that of synovial fluid. However, the underlying mechanism of this critical functional interaction remains unknown. The short-term objective of my program proposed here is to elucidate the composition-structure-function relationship of synovial fluid’s cartilage boundary lubricants through the study of PRG4 interactions with itself and HA, using various structural forms of PRG4 and HA, both in solution and at a surface, and assessing cartilage boundary lubrication function. Sophisticated and complementary biomechanical, biochemical, and biophysical bioengineering methods will be used to i) evaluate the extent and mode of interactions of PRG4+HA in solution; ii) assess and quantify PRG4+HA complex formation on surfaces; and iii) determine the boundary lubricating function of PRG4+HA preparations at an articular cartilage-cartilage biointerface. This fundamental work is both novel and feasible, and will result in significant advances in biointerface science, biotribology, and bioengineering. The novelty lies in the experimental approach and use of complementary and sophisticated biochemical, biophysical, and biomechanical methods to elucidate the nature of the functional PRG4+HA interaction. This work is feasible due to my unique expertise and experience with PRG4 and articular cartilage boundary lubrication, the development of additional methods within the laboratory for the study of the PRG4+HA interaction, and the strong training environment and record of training highly qualified personnel. Completion of this work will result in significant advances in the fields of biointerface science, biotribology, and bioengineering by 1) contributing to the understanding of the structure-composition dependence of the functional PRG4+HA interaction, and therefore a fundamental joint lubrication mechanism; and 2) with respect to my overall research program, provide a framework for a broader exploration of fundamental mechanisms of biological lubrication, and potentially the development of new PRG4+HA containing biomaterials and/or biotherapeutic fluids in Canada.

生物界面是细胞，分子，组织或生物材料与其他组织或生物材料之间的接口。生物界面科学有助于理解分子与表面之间的相互作用。分子的相互作用及其在表面上产生的功能可能与溶液中的相互作用不同。生物界面是自然科学和（生物）工程的核心，对于许多领域的研究，包括生物生物生物学，至关重要。生物脱水学是对滑动生物表面的润滑，摩擦和磨损的研究，可洞悉生物润滑的基本机制。 我的研究计划的总体目的是了解相关生物界面和生物材料上蛋白聚糖4（PRG4，一种关键的生物边界润滑剂）的生物实物和生物物理特性的基本和调节机制。 人体软骨是体内的组织，其载荷相对于附属组织表面，因此在充满液体的腔中形成生物界面。软骨的显着低摩擦和低磨损特性是通过涉及软骨，周围滑液及其构成及其相互作用的多种润滑模式制备的。边界润滑是一种重要且操作的模式，在地表到表面接触中发生，并且表面分子提供润滑功能。滑液和软骨表面中存在的两个临界边界润滑剂分子是PRG4和透明质酸（HA）。两者都充当剂量依赖性软骨边界润滑剂，并且还起作用，可将摩擦降低到滑液附近的摩擦水平。但是，这种关键功能相互作用的基本机制仍然未知。 我在这里提出的计划的短期目标是通过研究PRG4与自身的相互作用和HA，使用各种结构形式的PRG4和HA，无论是在溶液和表面上，以及评估软骨边界润滑功能。精致和互补的生物力学，生化和生物物理生物工程方法将用于i）评估溶液中PRG4+HA相互作用的程度和模式； ii）评估和量化表面上的PRG4+HA复合物； iii）确定在关节软骨生物界面上PRG4+HA制剂的边界润滑功能。 这项基本工作既新颖又可行，并且将在生物界面科学，生物植物学和生物工程方面取得重大进展。新颖性在于实验方法和完整性和复杂的生化，生物物理和生物力学方法的使用，以阐明功能性PRG4+HA相互作用的性质。这项工作是可行的，这是因为我在PRG4和关节软骨边界润滑中的独特专业知识和经验，在研究PRG4+HA相互作用的实验室内开发了其他方法，以及训练高素质的人员的强大培训环境和记录。这项工作的完成将导致生物界面科学，生物脱水学和生物工程领域的重大进展。1）有助于理解功能性PRG4+HA相互作用的结构组成依赖性，因此是一种基本的关节润滑机制； 2）关于我的整体研究计划，为生物润滑的基本机制提供了更广泛的探索，并有可能开发加拿大含有生物材料和/或生物治疗液的新PRG4+HA。