Type I Collagen Nanomorphology in Relation to Disease, Tissue Hierarchy, and Fibrillogenesis.

Type I Collagen Nanomorphology;Atomic Force Microscopy;Chemistry;Science;Chemistry

Fang, MingLes, Clifford Michael ;

University of Michigan

关键词: Type I Collagen Nanomorphology;    Atomic Force Microscopy;    Chemistry;    Science;    Chemistry;   

Others  :  https://deepblue.lib.umich.edu/bitstream/handle/2027.42/97898/mifang_1.pdf?sequence=1&isAllowed=y

瑞士|英语

来源: The Illinois Digital Environment for Access to Learning and Scholarship

【 摘 要 】

Although the axial D-periodic spacing is a well-recognized nanomorphological feature of type I collagen fibrils, the existence of a distribution of values has been largely overlooked since its discovery seven decades ago. This dissertation begins with the development of a quantitative method to measure the D-periodic spacing of type I collagen fibrils using Atomic Force Microscopy coupled with a 2D Fast Fourier Transform approach. Recent quantitative characterizations supported that a 10 nm collagen D-spacing distribution is intrinsic to collagen fibrils in various tissues as well as in vitro self-assembly of reconstituted collagen. In addition, the distribution was altered in Osteogenesis Imperfecta and long term estrogen depletion. The need for fibril-to-fibril analysis was highlighted since it was the D-spacing distribution, not the D-spacing mean, that showed statistically significant differences in diseases. The observation of D-spacing distribution was further expanded to a higher hierarchical level by examining fibril D-spacing distribution in relation to the microscale tissue organization. In dermis, bone and tendon, one common structure motif of collagen at the micrometer scale is the organization of fibrils into bundles. It was found that in each tissue type, collagen fibril D-spacings within a single bundle were nearly identical, and frequently differing by less than 1 nm. The full 10 nm range in D-spacing values was attributed to different values at the bundle level, independent of species or tissue types. In order to better understand the origin of D-spacing distribution and its relationship with type I collagen self-assembly, surface-mediated collagen self-assembly as a function of substrate and incubation concentration was investigated.Collagen fibril assembly on phlogopite and muscovite mica, as well as fibrillar gel coextrusion in glass capillary tubes, all exhibited D-spacing distributions similar to those commonly observed in biological tissues. The observation of D-spacing distribution by self-assembly of type I collagen alone is significant as it eliminates the necessity to invoke other pre-assembly or post-assembly hypotheses, such as variation in the content of collagen types, enzymatic cross-linking, or other post-translational modifications, as mechanistic origins of D-spacing distribution.