Mechanical and failure properties of lung and engineered tissues as a function of structural protein composition

Collagen and elastin, the main structural proteins of the extracellular matrix (ECM), impart distinct crucial mechanical properties to tissues in the body. These proteins are present in varying amounts in normal tissues, and the composition can be grossly affected by proteolytic diseases such as emphysema in the lung and aneurysm of blood vessel walls. Understanding how the composition of the ECM affects the mechanical properties of the tissue can lend insight into the development and progression of these diseases.; The goal of this project was to study how alterations in the structural protein composition of the ECM affect the mechanical and failure properties of various tissues. We studied quasi-static mechanical and failure properties in lung tissue strips from normal mice and two models of emphysema: elastase digestion of normal tissue and the genetic tightskin mouse, which spontaneously develops emphysema. We also investigated the changes in the mechanical and failure properties of ECM sheets engineered to contain varying amounts of collagen and elastin. Imaging methods were developed to measure the thickness of the tissues at various strains in order to estimate true stress. We found that tightskin lung tissue had a significantly higher Poisson ratio and significantly lower failure stress than normal tissue. Network modeling of the normal and tightskin tissue suggested that the increased Poisson ratio is due to structural deterioration and the decreased failure stress is related to decreased alveolar wall fiber stiffness accompanied by a decreased failure strain threshold. In the ECM sheets, we found that adding collagen to the ECM increased the stiffness. However, further increasing collagen content decreased the failure strain and altered matrix organization. We conclude that remodeling and elastolytic destruction of the lung during emphysema leads to conditions in which stresses akin to those during normal breathing can cause alveolar walls to fail, thereby contributing to the progression of the disease. In addition, in engineered replacement tissues, there is a trade-off between improved mechanical properties and decreased extensibility which can impact the effectiveness of these biomaterials since their performance relies on how well they match the mechanical properties of the native tissue.