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The Washington Research Foundation Fellowship
Jonathan McMichael, Bioengineering, 2010-11 WRFF
After looking for some time for the right fit in a research laboratory, I began studying cardiac muscle mechanics under Dr. Mike Regnier during my sophomore year. While my work initially involved examining muscle regulation through protein-protein interactions, these projects evolved into the larger scale I currently work with: whole muscle tissue. This year I will be working between Dr. Regnier’s lab and Dr. Margaret Allen’s lab at Benaroya Research Institute to develop an implantable scaffold to enhance healing in sites of skeletal muscle trauma. I truly appreciate the support of the Washington Research Foundation as I carry out my senior capstone design project.
In the constantly advancing biotechnology field, experience with technology rights and legal procedures is becoming increasingly valuable. Following my graduation this spring, I plan to pursue further education in bioengineering, as well as a strong foundation in the law. With these tools I hope to enter a career as a bioengineer with legal training, and work to commercialize new medical devices and technologies.
Mentor: Michael Regnier, Bioengineering
Project Title: Measurement of Force Development in Intact Cardiomyocytes
Abstract: The contractile properties of cardiomyocytes are altered in heart diseases such as hypertrophic (HCM) and dilated (DCM) cardiomyopathy. Past studies have been limited to protein-protein interactions and contractile properties of demembranated cardiac tissue or single myofibrils. Measurements from isolated intact cardiomyocytes are difficult because of cell size, fragility and difficulty in attaching cardiomyocytes to force measurement devices without damage. A method to successfully attach cells to force transducers and length changing motors would greatly benefit research in HCM, DCM and other cardiac diseases. I propose to develop an apparatus to measure force development in intact cardiomyocytes. The work will be approached in a series of three phases. In the first, glass microneedles will be designed to appropriate specifications to deflect under normal cardiomyocyte force. Microneedle design will be a recursive process, and will also include an examination of ideal shapes to achieve cell adhesion. Following this work, various adhesive materials will be characterized for their ability to withstand forces of the same magnitude as cardiac muscle cells. In addition to determining the most suitable adhesive, an electrical drive system will be designed to perturb cells for data collection by the instrument. The final project phase will be an application of the designed apparatus to intact cardiomyocyte infected with mutant forms of troponin C (the myofilament protein that binds calcium and triggers contraction) that mimics effects of HCM and DCM. Results are expected to clarify data previously collected from demembranated tissue and cell subunits. Importantly, it will allow us to extend studies to the coupling between calcium handling and myofilament contraction. Results will elucidate a novel method of quantifying force development in intact cells, and indicate further research directions toward the mediation of heart disease. Dr. Michael Regnier of the Department of Bioengineering will serve as primary mentor for this work.