Characterization of Type I Collagen and Osteoblast Response to Mechanical Loading
Abstract
Bone is a composite material made up of an inorganic (hydroxyapatite mineral) phase, a proteinaceous organic phase, and water. Comprising 90% of bone’s organic phase, type I collagen is the most abundant protein in the human body. Both hydroxyapatite and collagen contribute to bone mechanical properties, and because bone is a hierarchical material, changes in properties of either phase can influence bulk mechanical properties of the tissue and bone structure. Type I collagen in bone is synthesized by osteoblasts as a helical structure formed from three polypeptide chains of amino acids. These molecules are staggered into an array and the resulting collagen fibrils are stabilized by crosslinks. Enzymatic crosslinking can be limited by compounds such as β-aminopropionitrile (BAPN) and result in a crosslink deficiency characterizing a disease known as lathyrism. BAPN acts by irreversibly binding to the active site of the lysyl oxidase enzyme, blocking the formation of new crosslinks and the maturation of pre-existing immature crosslinks. Understanding how changes in bone properties on a cellular level transcend levels of bone hierarchy provides an opportunity to detect or diagnose bone disease before disease-related changes are expressed at the organ or tissue level. This dissertation studies the in vitro effect of BAPN-induced enzymatic crosslink reduction on osteoblast-produced collagen nanostructure, mechanical properties, crosslink ratio, and expression of genes related to type I collagen synthesis and crosslinking. The work also explores the effect of mechanical loading via applied substrate strain on these properties to investigate its potential compensatory impact.
Degree
Ph.D.
Advisors
Voytik-Harbin, Purdue University.
Subject Area
Biology|Biomedical engineering|Biomechanics
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