Microsystems for studying single heart cell mechanobiology
Abstract/Contents
- Abstract
- With each heart contraction, blood rushes throughout the expansive circulatory system providing oxygen and other nutrients to the body. Cardiomyocytes are the contractile units responsible for these contractions. In the event of ischemia, the heart reduces its contractile output and loses a significant number of cardiomyocytes. In the ischemic region of the heart, the tissue remodels and the mechanical properties differ significantly from healthy tissue. Due to the limited regeneration capabilities of the heart, recent focus has been on understanding how the reintegration of pluripotent-derived cardiomyocytes can help restore contractile function. These pluripotent-derived cardiomyocytes will need to survive in mechanically active environments and contribute to the contractile output of the heart. However, even before these cardiomyocytes can be used, we need to develop an understanding for how primary immature cardiomyocytes should respond to mechanical forces in vitro. This work explores cardiomyocyte contractile ability in the presence of mechanical forces. For this work, we investigate neonatal murine cardiomyocytes. We begin by developing a protein patterning technique suitable for polyacrylamide. With this technique, we achieve repeatable arrays of neonatal cardiomyocytes and control their shape and size. We found this technique improves sarcomere distribution, making them look more mature and like adult cardiomyocytes. Using micro-tools, we then investigate cardiomyocyte contractility in the presence of mechanical forces. These findings suggest that the Frank-Starling law that governs the heart is also applicable to neonatal cardiomyocytes. Later in this work, we introduce the MEMS tool developed to better understand cardiomyocyte contractile forces. We describe the design goals and fabrication process of the micro-device. In addition, we present the calibration and testing results, and demonstrate that this device provides a reliable and alternative way to calibrate substrates used to study contractile forces. In the closing section of this work, we introduce ideas for future studies building on this work, and the work of others.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2013 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Higgs, Gadryn Christopher | |
|---|---|---|
| Associated with | Stanford University, Department of Mechanical Engineering. | |
| Primary advisor | Pruitt, Beth | |
| Thesis advisor | Pruitt, Beth | |
| Thesis advisor | Kenny, Thomas William | |
| Thesis advisor | Levenston, Marc Elliot | |
| Advisor | Kenny, Thomas William | |
| Advisor | Levenston, Marc Elliot |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Gadryn Christopher Higgs. |
|---|---|
| Note | Submitted to the Department of Mechanical Engineering. |
| Thesis | Thesis (Ph.D.)--Stanford University, 2013. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2013 by Gadryn Christopher Higgs
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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