Glucosepane is associated with changes to structural and physical properties of collagen fibrils

Collagen glycation, and in particular the formation of advanced glycation end-product (AGE) crosslinks, plays a central role in the ageing process and in many of the long-term complications of diabetes. Glucosepane, the most abundant and relevant AGE crosslink, has been suggested to increase the stiffness of tissue and reduce its solubility, although no evidence is available concerning the mechanisms. We have used a combination of computational and experimental techniques to study a collagen-rich tissue with a relatively simple organisation to further our understanding of the impact of glucosepane on the structural and physical properties of collagen fibrils. Our work shows that glucosepane levels increase dramatically in aged tendon tissue and are associated with the reduced density of collagen packing and increased porosity to water molecules. Our studies provide the basis to understand many of the tissue dysfunctions associated with ageing and diabetes across a range of different tissues types