The extracellular matrix (ECM), as the native cellular substrate, provides necessary mechanical and biological signals to cells. Cells exert forces in the nanonewton range, which when applied over time can strain extracellular matrix fibers until breakage. Cells and tissues inherently interact mechanically with their surrounding matrix, so tissue engineering materials would benefit from the ability to fully exploit mechanical-biochemical interactions to enhance integration with the human body. In this work, I developed an increased understanding of ECM fiber mechanical and mechano-biochemical properties. First, I generated novel composite ECM fibers that can be used to study combinations of ECM proteins in a controlled way. I determined how protein composition impacts mechanical properties of novel single ECM fibers in a hydrated state and showed how mechanical properties can be tuned through composition. Next, I assayed for strain and heparin-sensitive allosteric binding of ligands to fibronectin and fibrin fibers, and determined that the binding of two key growth factors is impacted by strain and heparin. Finally, I investigated the impact of fiber strain, heparin-pretreatment, and growth factor interactions on endothelial cell migration. The novel contributions of this project are the generation of new composite extracellular matrix fiber types with tunable mechanical properties, as well as the identification of extracellular matrix protein mechanosensitive and heparin-sensitive interactions with growth factors and their impact on endothelial cell migration, which could be used to aid in the design of protein-based biomaterials for cardiovascular applications. / 2024-05-23T00:00:00Z
| Identifer | oai:union.ndltd.org:bu.edu/oai:open.bu.edu:2144/44767 |
| Date | 23 May 2022 |
| Creators | Hoffmann, Gwendolyn A. |
| Contributors | Smith, Michael L., Wong, Joyce Y. |
| Source Sets | Boston University |
| Language | en_US |
| Detected Language | English |
| Type | Thesis/Dissertation |
| Rights | Attribution-NonCommercial-ShareAlike 4.0 International, http://creativecommons.org/licenses/by-nc-sa/4.0/ |
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