New insights into collagen superstructure assembly and interactions with the extra-cellular matrix

Collagen is the most abundant protein in animals, and plays a major role in maintaining tissue structure and integrity. Molecules of this protein associate to form two common types of complex structures, fibres and networks, which become major components of skin, bones, tendons, cartilage, and other tissues. In addition to its natural functions, collagen is used as scaffolding in engineering tissues for transplant, and as a biological material to coat artificial implants to decrease the chance of rejection by the body. When forming structures, collagen molecules have been shown to align, essentially always, in the same relative direction. Further, collagen structures have been shown to have some self-repair ability if improper structure formation occurs. Improper formation has been implicated in pathological conditions including cancer in nervous tissue, atherosclerotic plaques, Hodgkin's disease, and silicosis. Regardless of the importance of collagen, many aspects of its assembly remain unknown. Collagen proteins feature structural regions that are highly rigid and others that are flexible. I hypothesize that the presence of flexible regions allows for proper alignment of collagen molecules during growth, and for the self-repair ability of collagen. To examine this hypothesis, I will use a high-resolution molecular imaging technique, atomic force microscopy (AFM), to search for common structural details in flexible regions. AFM is also capable of measuring the force of interaction between molecules, and I will take advantage of this to measure the strength of interaction between collagen molecules and other partners. My research will allow for improved use of collagen as a material for implants or transplants. Identification of molecules which interact strongly with collagen, and the mechanisms by which these interactions occur, will assist in the design of drugs capable of specifically treating disorders associated with improper collagen structure formation.