Minor Fibril-Forming Collagens: Key Regulators of Collagen Fibrillar Structure and Biomechanics
Thursday, August 1, 2019
1:30 PM-3:30 PM
BIOMED PhD Research Proposal
Title:
Minor Fibril-Forming Collagens Are the Key Regulators of Collagen Fibrillar Structure and Biomechanics in Cartilaginous Tissues
Speaker:
Chao Wang, PhD Candidate
School of Biomedical Engineering, Science and Health Systems
Drexel University
Advisor:
Lin Han, PhD
Associate Professor
School of Biomedical Engineering, Science and Health Systems
Drexel University
Details:
In the knee joint, articular cartilage and meniscus work synergistically to enable daily activities such as walking, running, and jumping. Although injuries of these two tissues are common, the statement “once it's destroyed, it never repairs” still holds true since three centuries. This can be attributed to both the tissues’ poor capability of intrinsic repair due to their non/low vascularity, innervation, and very low cellular mitotic activity. To this day, the regeneration of both tissues remains elusive, partially because we lack a comprehensive understanding of the complex hierarchical matrix architecture, the functions of the individual matrix component, as well as the molecular activities that regulate the matrix assembly and the cellular behavior of both tissues.
To address these limitations, the proposal will query the roles of two fibril-forming collagens in regulating the assembly of fibrous and cartilaginous tissues, and their impact on the micro-mechanical environment and mechano-response of residing cells. First, we will study the Col3a1 heterozygous (Col3a1+/-) murine model to assess the collagen fibril structure and micro-mechanical properties of both cartilage and meniscus during early skeletal maturation. The new findings will inform the design of cartilaginous tissue regeneration by modulating the activity and availability of collagen III. Second, we will identify the specialized composition, structure, and mechanical properties of the pericelluar matrix (PCM) in normal meniscus, the micro-domain where the initial collagen fibrillogenesis takes place.
We will use the Col5a1 heterozygous (Col5a1+/-) murine model to assess its fibril structure and micro-mechanical properties during post-natal growth, and test the impact of collagen V on the strain transmission function of the PCM in mediating fibrochondrocyte mechano-transduction. Studying the PCM will advance current understanding and lay the foundation for future studies of the roles of minor fibril-forming collagens, yielding new targets for early detection and intervention of knee joint osteoarthritis (OA). In addition, the focus of collagen III and V will broaden the fundamental knowledge of Ehlers-Danlos syndrome (EDS), a human genetic disorder with a prevalence ratio of 1:5,000. Haplodeficiencies of collagen III and V are the direct causes of two common EDS sub-types, the vascular EDS (vEDS) and classic EDS (cEDS), respectively.
Contact Information
Ken Barbee
215-895-1335
barbee@drexel.edu