Engineering the microenvironment at the protein-hydrogel interface to investigate the role of the extracellular matrix protein type in single cell cardiomyocyte structure and function
Abstract/Contents
- Abstract
- I developed hydrogel platforms to investigate the role of the extracellular matrix (ECM) proteins on cardiomyocyte structure and function. The biochemical and biophysical properties of the microenvironment are known to play a key role in cell structure and function. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) hold great potential as a model to expand our knowledge of human heart muscle cells and their interactions with the surrounding microenvironment. In this thesis, I provide an introduction to cardiomyocytes and the role of the microenvironment properties in modulating cardiomyocyte structure and function. I present the gap in technologies that have been used to manipulate the protein-hydrogel interface (Chapter 1). I provide an in-depth review of the changes of native cardiomyocyte adhesion molecules and ECM composition throughout cardiac development and disease (Chapter 2). I provide an in-depth review of in-vitro platforms for cardiomyocyte structural and function assessment (Chapter 3). I discuss the development of our protocol which consists of a combination of lift-off protein patterning, a covalent protein-hydrogel linker, and the copolymerization protein transfer technique. We show that we are able to tune the ECM protein type across a wide variety of proteins including a mixture of ECM proteins, individual proteins, engineered biomaterials, and cell-cell adhesion proteins (Chapter 4). Next, I present traction force microscopy data comparing the hiPSC-CM morphology and contraction force on laminin versus fibronectin, with Matrigel as a positive control (Chapter 5). Last, I provide a summary of my findings, future platform development areas, and discuss future research directions my PhD work enables (Chapter 6). I provide ideas for how my hydrogel platforms could be implemented to study cardiac disease with interstitial fibrosis or cardiomyocytes with mutations in the cell adhesion molecules.
Description
| Type of resource | text |
|---|---|
| Form | electronic resource; remote; computer; online resource |
| Extent | 1 online resource. |
| Place | California |
| Place | [Stanford, California] |
| Publisher | [Stanford University] |
| Copyright date | 2021; ©2021 |
| Publication date | 2021; 2021 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Castillo, Erica Araceli |
|---|---|
| Degree supervisor | Kenny, Thomas William |
| Thesis advisor | Kenny, Thomas William |
| Thesis advisor | Heilshorn, Sarah |
| Thesis advisor | Pruitt, Beth |
| Degree committee member | Heilshorn, Sarah |
| Degree committee member | Pruitt, Beth |
| Associated with | Stanford University, Department of Mechanical Engineering |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Erica Araceli Castillo. |
|---|---|
| Note | Submitted to the Department of Mechanical Engineering. |
| Thesis | Thesis Ph.D. Stanford University 2021. |
| Location | https://purl.stanford.edu/kd190jy9988 |
Access conditions
- Copyright
- © 2021 by Erica Araceli Castillo
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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