AFM Investigations of Collagen Fibril Structure in the Murine Adventitia

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Date

2016-12

Authors

Albert, Benjamin

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The Ohio State University

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Abstract

Collagen fibrils in the extracellular matrix (ECM) maintain mechanical properties of blood vessels and act as binding sites for various proteins. In the blood vessels, the adventitial layer is mainly comprised of fibrils of collagen types 1 and 3. Previous studies have shown that the amount of collagen deposited can be affected by the expression of certain collagen-binding proteins (CBP), mutations in the collagen polypeptide chains and additional factors accompanying pathogenesis of vascular diseases. Few studies have been done to elucidate the changes in structural features of these collagen fibrils. This study investigates changes collagen fibrils in the murine adventitia. Studies were performed ex-vivo on tissues extracted from mice lacking a CBP, discoidin domain receptor 1 (DDR1) and in a model of abdominal aortic aneurysm (AAA). Atomic force microscopy (AFM) was used to characterize the D-periodicity of collagen fibrils by measuring both the length of the D-period and the depth of the gap in the D-period. Our results show that the depth of the D-period in DDR1 KO mice was significantly greater than those in WT mice, but the length showed no significant difference. Collagen fibrils in AngII-infused ApoE models of AAA exhibited both normal and abnormal fibril characteristics. No significant differences in the depth or length of D-period was observed in normal collagen fibrils in AAA models as compared to saline-infused controls. However, the abnormal collagen fibrils in AAA revealed a complete lack of D-periodic depth as compared to normal fibrils. These results make the case that changes in the depth of D-periods in the collagen fibril a manifestation of the ECM environment and could be used to understand the pathogenesis of the disease.

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Atomic Force Microscopy, Collagen, DDR1, Abdominal Aortic Aneurysm

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