CAREER: Hyaluronan-Protein Networks in Solution and in the Polymer Coat of Cells

Georgia Tech Research Corporation, Atlanta GA

Investigators

Abstract

This Career award by the Biomaterials program in the Division of Materials Research to Georgia Institute of Technology is to study the mechanistic understanding of the link between the properties of hyaluronan (HA)-rich materials and biological functions. A number of advanced micro-characterization techniques that are rarely used in cell biology studies will be applied in this study, including passive microrheology, fluorescence recover after photobleaching, optical force probe microscopy and osmotic pressure studies. These biophysical and soft condensed matter tools will be used for a systematic investigation of the structural properties (network architecture, heterogeneity, mesh size, bundling, shape) and mechanical properties (compressibility, loss and storage moduli) of two major categories of HA-protein systems. In a first thrust, model HA-protein solutions will be used to investigate HA interactions with versican, a protein found in the extracellular matrix, and with the presumptive HA crosslinking proteins TSG-6, heavy chain and PTX-3. The second thrust directly tackles the pericellular coat, a HA-protein network anchored to many cell surfaces. Recent studies have indicated that mechanical and topographical features of HA-protein structures imparts onto its biological environment a diverse range of structural and viscoelastic properties with far-reaching consequences for cell physiology and pathology such as fertilization, cell migration, inflammation, and cancer metastasis. Overall, this project is expected to provide both a very fundamental scientific knowledge in biomaterials and cell biology. As part of the outreach activities, these research studies will be integrated into the Direct to Discovery program at Georgia Tech that provides seamless video conferencing between researchers and classrooms using Georgia?s Peach Net high-speed internet infrastructure, and working closely with a designated teacher in a rural, socioeconomically-disadvantaged community to develop new teaching and training modules. Hyalrunon polymer plays an important role in many body functions - both physiological and pathological - such as lubricating fluid in cartilage, fertilization of human egg, joint inflammation and spread of cancer. Yet, very little is known about these various hyaluronan architectures, and their functions and properties. Using novel tool and approaches, this project is expected to provide both fundamental scientific knowledge of this biomaterial and cell biology, while simultaneously providing new insights to a material whose therapeutic use is well established. As part of the outreach program and working closely with a designated teacher in a rural, socioeconomically-disadvantaged community, this research project will be integrated into the Direct to Discovery (D2D) program at Georgia Institute of Technology that provides seamless video conferencing between researchers and classrooms using Georgia?s Peach Net high-speed internet infrastructure. Modules will be designed to combine the teacher?s lecture material with (virtual) visits to the PIs Lab using D2D technology, giving students an opportunity to explore cell culture, study viscoelastic properties of materials, and use of different experimental tools ? all the while reaching educational goals to learn topics such as the ?structure and function of cells?, ?nature of matter?, and ?conceptual laws of forces?.