Although extracellular matrix (ECM) composition and organization are considered important regulators of cardiomyocyte phenotype in vitro and in vivo, a causal relationship between the ECM structure and effect on maintenance of cardiomyocyte (CM) phenotype has not been established. In this study, we investigated how key structural characteristics of electrospun scaffolds (fiber alignment, spacing, and diameter) regulated CM phenotype specifically cell morphology, actin/myosin patterning, and cardiac gene expression. We found that aligned fiber scaffolds resulted in a longer, more rod shaped morphology in both neonatal and adult CMs. Along with better morphology, CMs were also found to have better-organized cell actin/myosin bands and cardiac specific gene expressions of β-MYH7 and SCN5A.1 and SCN5A.2 in both neonatal and adult cells. Additionally, upon exposure to variously spaced aligned fibers, adult CM action/myosin structure and morphology did not change but the overall orientation of the cells, relative to the fibers, increased from 45° to parallel as fiber spacing increased from 2 µm to 15µm. These findings provide critical insights into ECM-CM interactions that are responsible for maintenance/loss of neonatal and adult cardiomyocyte phenotype, and highlight the importance of developing more relevant cardiomyocyte culture substrates for in vitro studies.
| Identifer | oai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-07252014-110513 |
| Date | 26 July 2014 |
| Creators | Rath, Rutwik |
| Contributors | Douglas B. Sawyer, M.D., Ph.D., Hak-Joon Sung, Ph.D. |
| Publisher | VANDERBILT |
| Source Sets | Vanderbilt University Theses |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.vanderbilt.edu/available/etd-07252014-110513/ |
| Rights | unrestricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to Vanderbilt University or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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