| Summary: | Thesis (Ph.D.)--Boston University === The dynamic mechanical behavior of arteries is essential to a properly functioning vascular system. Within the arterial extracellular matrix (ECM), the organization of collagen and elastin leads to the bulk of the passive mechanical behavior of the tissue. While remodeling of the ECM occurs naturally in healthy arteries to maintain normal functioning, vascular diseases often create different chemical and mechanical conditions that cause significant changes in structure and adverse effects on the mechanical behavior. The goal of this dissertation is to understand the roles of the ECM components in the mechanical behavior of vascular tissues, and how mechanical and biological interactions change during disease.
Our study of in vivo obstruction induced pulmonary artery remodeling suggests clinically relevant relationships between the mechanical integrity and biochemical composition of the tissue. Arteries had earlier collagen engagement and increased tissue stiffness due to higher collagen content. An in-vitro treatment with elastase leads to lamellae fragmentation and a faster rate of degradation when tissues were digested under stretch. We have shown for the first time the transition from J-shaped to S-shaped stress-strain behavior in arteries undergoing elastin degradation. This potential for large stretches with minimal increases in pressure could occur as aortic tissue becomes dilated during the formation of aneurysms. Multiphoton imaging during mechanical loading shows that elastin and collagen in the medial and adventitial layers are recruited differently. In the unloaded state, elastin fibers are pre-stretched and apply compressive forces on collagen fibers contributing to their crimping. Upon loading, medial elastin fibers are immediately recruited while the adventitial collagen fibers engage and become the major load-bearing component when strain reaches 20-25%. In contrast medial collagen is engaged throughout loading. After significant removal of elastin, the second harmonic generation suggests collagen fibers become straightened and aligned leading to earlier recruitment and rapidly stiffened mechanical behavior. This microstructural and mechanical information can be applied to constitutive models for prediction of tissue mechanics where collagen and elastin are the major load bearing components. Our study shows that the interactions between the elastin and collagen structure determine the mechanics of arteries and carry important implications to vascular mechanobiology.
|
|---|
