Abstract:

X-ray fiber diffraction (XRD) is a powerful tool to study structure of large molecular aggregates within tissues. It may reveal molecular conformation of tissue components, their arrangement in space and effect of some inorganic or biochemical reagents on fiber structure and tissue integrity.

Collagen fibrils are the most important structural elements of various connective tissues, including ligaments, tendons, cartilage, and cardiac valves and chordae tendineae. Previously, many aspects of the triple-helical collagen structure and its interactions have been examined via standard biochemical techniques. However, these studies mainly addressed only the properties of single collagen molecules or even their fragments in solution. Collagen fibrils possess specific structural parameters, which depend on collagen type, ECM components and mechanical load, and these differ from tissue to tissue. Combination of x-ray diffraction and XFM, developed at BioCAT, electron microscopy, and 'fibril biochemistry' helps better characterize the collagenous matrix in terms of these parameters. Most importantly, understanding the molecular organization in collagen fibrils and the availability of key binding and cleavage sites and their changes in response to certain chemicals and mechanical overload may explain the pathological tissue changes that occur in trauma and in diseases such as heart disease and arthritis.

Moreover, combined XRD-XFM approach can be used to explore other interesting fibrous systems and pathologies, such as nerve tissue demyelination, nephrogenic systemic fibrosis and variety of artificial tissues.