Investigating the molecular basis of collagen's finely tuned stability with single-molecule manipulation techniques
Collagen is the fundamental structural protein in our bodies, which means changes in its chemical composition can have profound, widespread effects on health. For example, connective tissue diseases, the leading cause of disability and absence from work in Canada, can be caused by a change affecting only one position out of 1000 in the DNA sequence that codes for collagen. As we age, collagens in our body tissues become chemically modified, leading to structural changes that result in weakening of bone structure and the deterioration of joints, arteries and the retina, a situation that is exacerbated by diabetes. The controlled production and degradation of collagen is important for normal embryo development; a breakdown in this controlled pathway is also associated with the spread of cancerous tumors in the body. All of these health-related problems are related to chemical changes in collagen, which lead to changes in its structural and elastic properties at the tissue level. Dr. Nancy Forde is studying the elastic properties and stability of single collagen molecules, to identify the relationship between chemical changes and changes in the structure and function of collagen. Her team is employing the world’s smallest tweezers, optical and magnetic tweezers, to grab, stretch and twist single collagen proteins. This special equipment is currently applied to protein study at only a handful of labs worldwide. Dr. Forde and her team are directing their efforts to better understand how changes in collagen at the molecular level affect the elastic and structural properties of tissues. This research could help explain how tissues deteriorate with age, as well as the impact of these changes on the development and severity of diseases such as cancer and diabetes.