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

点击翻译按钮获取中文摘要

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.