An aneurysm of the aorta is a common pathology characterized by segmental weakening of the artery. Although it is generally accepted that the vessel-wall weakening is caused by an impaired collagen metabolism, a clear association has been demonstrated only for rare syndromes such as the vascular type Ehlers-Danlos syndrome. Here we show that vessel-wall failure in growing aneurysms of patients who have aortic abdominal aneurysm (AAA) or Marfan syndrome is not related to a collagen defect at the molecular level. On the contrary our findings indicate similar (Marfan) or even higher collagen concentrations (AAA) and increased collagen cross-linking in the aneurysms. Using 3D confocal imaging we show that the two conditions are associated with profound defects in collagen microarchitecture. Reconstructions of normal vessel wall show that adventitial collagen fibers are organized in a loose braiding of collagen ribbons. These ribbons encage the vessel, allowing the vessel to dilate easily but preventing overstretching. AAA and aneurysms in Marfan syndrome show dramatically altered collagen architectures with loss of the collagen knitting. Evaluations of the functional characteristics by atomic force microscopy showed that the wall has lost its ability to stretch easily and revealed a second defect: although vascular collagen in normal aortic wall behaves as a coherent network, in AAA and Marfan tissues it does not. As result, mechanical forces loaded on individual fibers are not distributed over the tissue. These studies demonstrate that the mechanical properties of tissue are strongly influenced by collagen microarchitecture and that perturbations in the collagen networks may lead to mechanical failure.A ortic aneurysms are localized dilatations of the aortic wall that are caused by segmental weakening of the vessel wall. Although aneurysms generally are without clinical symptoms, larger aneurysms may rupture, and bleeding from a ruptured aneurysm is responsible for more than 15,000 annual deaths in the United States alone (1).Aneurysm formation relates to a primary or secondary (acquired) defect in the matrix structures supporting the vessel wall resulting in attenuation and ultimate failure of the vessel wall (2). Although extensive loss of medial elastin traditionally is considered the hallmark of aneurysm formation, it now is acknowledged that aneurysmal growth and ultimate rupture relate to impaired collagen homeostasis (2). Remarkably, although numerous studies have looked for putative quantitative changes in aortic collagen, results reported to date are controversial (3-5). With the exception of rare mutations in the collagen III gene such as the vascular type of Ehlers-Danlos syndrome, no clear association between impaired collagen homeostasis and aneurysm growth and/or rupture has been identified.In search of the collagen defect(s) underlying aneurysm formation, we applied an integrated approach of biochemical analyses, multiple imaging modalities, and functional analysis by atomic force microscopy (AFM) to...

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Patterning photoresist with extreme control over dose and placement is the first crucial step in semiconductor manufacturing. However, how can the activation of modern complex resist components be accurately measured at sufficient spatial resolution? No exposed nanometre-scale resist pattern is sufficiently sturdy to unaltered withstand inspection by intense photon or electron beams, not even after processing and development. This paper presents experimental proof that infrared atomic force microscopy (IR-AFM) is sufficiently sensitive and gentle to chemically record vulnerable yet valuable lithographic patterns in a chemically amplified resist after exposure prior to development. Accordingly, IR-AFM metrology provides long-sought insights into changes in the chemical and spatial distribution per component in a latent resist image, both directly after exposure and during processing. With these to-be-gained understandings, a disruptive acceleration of resist design and processing is expected.