Title: "Mechanically Active and Tunable Extracellular Matrix Fibers"
Michael Smith, PhD – BU BME (Co-Advisor, Chair)
Joyce Wong, PhD – BU BME (Co-Advisor)
Katherine Zhang, PhD – BU ME
Matthew Layne, PhD – BUSM Biochemistry
The extracellular matrix (ECM), as the native cellular substrate, provides necessary mechanical and biological signals to cells. Tissues inherently interact mechanically with their surrounding matrix, but tissue engineering materials have not fully exploited this interaction to enhance integration with the human body. We propose to develop an increased understanding of ECM mechanical and mechano-biochemical properties in order to design mechanically actuated release of proteins from mechanically tunable ECM fibers. To achieve this goal, we will determine how composition impacts mechanical properties of wet spun ECM fibers in both dry and hydrated states. We will use ECM fibers bound to stretchable membranes to assay for strain-sensitive binding of ECM ligands to the fibers, and determine the impact of these interactions on cell behavior and phenotype. Finally, we will generate a chimeric protein combining a strain-sensitive binding domain with a therapeutic protein for mechanically actuated release of proteins from ECM fibers. This project will contribute to basic knowledge of extracellular matrix fiber mechanical properties, extracellular matrix protein mechanosensitive interactions, and demonstrate the use of native ECM interactions for protein release from a material, which could be used in cardiovascular tissue engineering applications such as vascular grafts.