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Multi-scale analysis of morphology, mechanics, and composition of collagen in murine osteogenesis imperfecta

By Zachary Ryan Bart

Abstract

Indiana University-Purdue University Indianapolis (IUPUI)Osteogenesis imperfecta is a rare congenital disease commonly characterized by brittle bones caused by mutations in the genes encoding Type I collagen, the single most abundant protein produced by the body. The murine model (oim) exists as a natural mutation of this protein, converting its heterotrimeric structure of two Col1a1 molecules and a single Col1a2 molecule into homotrimers composed of only the former. This defect impacts bone mechanical integrity, greatly weakening their structure. Femurs from male wild type (WT), heterozygous (oim/+), and homozygous (oim/oim) mice, all at 12 weeks of age, were assessed using assays at multiple length scales with minimal sample processing to ensure a near-physiological state. Atomic force microscopy (AFM) demonstrated detectable differences in the organization of collagen at the nanometer scale that may partially attribute to alterations in material and structural behavior obtained through mechanical testing and reference point indentation (RPI). Changes in geometric and chemical structure through the use of µ-Computed Tomography and Raman spectroscopy respectively indicate a smaller, brittle phenotype caused by oim. Changes within the periodic D-spacing of collagen point towards a reduced mineral nucleation site, supported by reduced mineral crystallinity, resulting in altered material and structural behavior in oim/oim mice. Multi-scale analyses of this nature offer much in assessing how molecular changes can compound to create a degraded, brittle phenotype

Topics: Atomic force microscopy, Raman spectroscopy, Reference point indentation, MicroCT, crystallinity, modulus, Osteogenesis imperfecta, Osteogenesis imperfecta -- Genetic aspects, Raman spectroscopy, Atomic force microscopy, Geometric tomography -- Research, Nanotechnology, Microtechnology -- Testing, Spectroscopic imaging, Biomedical engineering, Collagen
Year: 2013
OAI identifier: oai:scholarworks.iupui.edu:1805/3654
Provided by: IUPUIScholarWorks

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