Although it is well established that in both Type 1 and Type 2 diabetes arterial stiffening occurs, the differential roles played by constitutive arterial components remain unknown. Here, we characterised the nano-mechanical properties of fibrillin microfibrils, a key elastic fibre component, extracted from diabetic arteries.

We isolated fibrillin microfibrils from the aortae of rats with a Streptozotocin-induced model of Type 1 diabetes, and age-matched controls. Fibrillin microfibrils have a ‘beads-on-a-string’ structure with a periodicity of approximately 56nm. Atomic force microscopy (AFM) was used to image the microfibrils to determine whether there were any structural changes. Molecular combing was also used to apply a known tensile force (4000 pN) to partially adsorbed fibrillin microfibrils. Combed microfibrils were also imaged with AFM.

Fibrillin microfibril periodicity was significantly reduced in the diabetic rats; 52.7 +/− 0.3nm (diabetic) compared with control animals; 59.5±0.4nm (n=1500 periodicity measurements, 3 animals per group; p<0.01). Following combing, periodicity was significantly increased in microfibrils isolated from diabetic aortae (62.3nm, SEM 0.51nm, t-Test, N=1500, P<0.01) as compared with control animals (58.5nm, SEM 0.40nm, p<0.001, t-test).

Eight weeks after islet cell destruction and hyperglycaemia, in vivo, profound changes in microfibril structure are induced, which in turn appear to weaken these important macro-molecular assemblies. This study also demonstrates that it is possible to localise structural and mechanical changes in diabetic aortae at the nanoscopic length scale.