Effects of aging and diabetes on the deformation mechanisms and molecular structural characteristics of collagen fibrils under daily activity

Crosslinking plays an important role in collagen-based tissues since it affects mechanical behavior and tissue metabolism. Aging and diabetes affect the type and density of crosslinking, effectively altering tissue properties. However, most studies focus on these effects under large stress rather than daily activities. We focus on the deformation mechanisms and structural change at the binding sites for integrins, proteoglycans, and collagenase in collagen fibrils using a fully atomistic model. We show that high-connectivity enzymatic crosslinking (our HC model, representing normal tissues) and advanced-glycation end-products (our Glucosepane model, which increase in diabetes) result in uniform deformation under daily activity, but low-connectivity enzymatic crosslinking (our LC model, representing aging tissues) does not. In particular, the HC model displays more sliding, which may explain the ability of healthy tissues to absorb more strain energy. In contrast, AGEs induce instability in the structures near the binding sites, which would affect the tissue metabolism of the collagen molecule. Our results provide important insights into the molecular mechanisms of collagen and a possible explanation for the role of crosslinking in tissues undergoing daily activity.

Automated summary

Crosslinking affects the mechanical behavior and tissue metabolism of collagen-based tissues. Aging and diabetes alter the crosslinking type and density, thus changing tissue properties. High-connectivity enzymatic crosslinking and advanced-glycation end-products result in uniform deformation under daily activity, while low-connectivity enzymatic crosslinking does not. High-connectivity model displays more sliding, while AGEs induce instability in structures near the binding sites.