The human eye is filled with a vitreous gel that becomes progressively more fluid-like with age. The gel is a composite material composed of a network of stiff collagen fibers and flexible polysaccharide chains in an aqueous solution. This project will explore the relationships between the structure of the gel and its mechanical and thermodynamic properties in order to understand how changes in those properties are correlated with vision impairment. The project will address these relationships by studying a reconstituted gel made of the primary components of the vitreous material. The team of investigators will use a variety of experimental and theoretical methods to develop a quantitative understanding of the mechanical properties of the network and the thermodynamics of the reconstituted gel. The results of the study will provide insight into the mechanical origin of vitreous related pathologies and may provide guidance into effective therapeutic strategies to treat vision disorders. Results from the project will be used in courses for university students in biophysics and related fields. The team of investigators will participate in several outreach activities that encourage the participation of students, especially those from underrepresented groups, in science and engineering subjects. In addition, the team will participate with high school teachers in summer workshops to emphasize the importance of high-school mathematics as a foundation for success in college studies and professional careers.
The investigators will characterize experimentally the microrheology of the primary components of vitreous gel using purified extracts of hyaluronic acid, type II heterotypic collagen network, and reconstituted composites made of the collagen network and hyaluronic acid. They will use a combination of experimental and theoretical approaches to construct a mechanical phase diagram of reconstituted gel that can be used to relate material properties to structure, micromechanics, and concentrations of hyaluronic acid and collagen. They will construct a thermodynamic phase diagram of the reconstituted gel using experimental and analytical methods to investigate the sol-gel, gel collapse, and complex coacervation transitions in mixtures of hyaluronic acid and collagen. Finally, they will establish connections between changes in mechanical and thermodynamic properties of the reconstituted vitreous gel and pathological changes that lead to vision problems. The project will fill a gap in our understanding of how material properties of vitreous gel are quantitatively related to its macromolecular organization and to different types of environmental cues. It will provide important insights into changes in the vitreous gel with age or with onset of ocular pathologies. Results of the project may apply broadly to other materials such as soft biological tissues and biomimetic hydrogels.
