Role of perifibrillar proteins in collagen fibril assembly, fibril interactions and matrix remodelling

• Applicant: Professor Dr. Frank Zaucke
• Subject Area: Orthopaedics, Traumatology, Reconstructive Surgery
• Term: from 2011 to 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 190038206

The cartilage extracellular matrix contains two major suprastructures, namely the fibrillar collagenous network and gel-like aggrecan complexes. In order to guarantee tissue stability and function a mutual interaction between these two supramolecular compartments is required. This is achieved by a set of molecules present on the collagen fibril surface, the so-called perifibrillar proteins. These proteins and proteoglycans are often organized in higher order complexes. Their biological relevance is underlined by the fact that mutations in their encoding genes can lead to chondrodysplasias or predispose for degenerative diseases, such as osteoarthritis. In the current project, we will characterize the role of perifibrillar proteins in fibril assembly, fibril interactions and matrix remodelling. Protein biochemistry, electron microscopy, chondrocyte culture and mouse models deficient in perifibrillar proteins will be employed to analyze individual components and their contribution to the overall structure and function of adaptor complexes. This will give insight into the role of perifibrillar proteins in cartilage homeostasis during normal development and possibly into mechanisms involved in cartilage diseases.

• DFG Programme: Research Grants