Nano-scale mechanisms of AGEs in mineralized collagen fibrils

Determine the nano-scale mechanisms by which advanced glycation end-product (AGE) cross-linking within mineralized type I collagen fibrils governs deformation, stiffening, and fracture behavior, and assess how these mechanisms contribute to increased brittleness observed in diabetic bone despite normal or elevated bone mineral density.

Background

Type 2 diabetes is associated with increased bone fragility even at normal or slightly elevated bone mineral density. Advanced glycation end-products accumulate in collagen and are correlated with increased brittleness and reduced deformation capacity.

Prior work has clarified how AGEs affect non-mineralized fibrils, but bone fibrils are mineralized. The specific nano-scale mechanisms by which AGEs alter the mechanics of mineralized collagen fibrils remain unresolved and are essential to link molecular changes to tissue-level fragility.