Engineered protein hydrogels to study neural niche interactions
Abstract/Contents
- Abstract
- The native extracellular matrix (ECM) provides both biophysical and biochemical cues that modulate cellular behaviors, including maintenance of homeostasis and tissue repair following injury. Carefully controlled ECM mimics can permit detailed studies of cell-niche interactions, providing design criteria for engineering solutions to various medical challenges. This dissertation begins with a review of the microenvironmental properties known to regulate stem cell behavior and discusses how these properties can be controlled in hydrogel-based systems. The next chapters present strategies to introduce bio-orthogonal crosslinking chemistries into engineered protein hydrogels while retaining independent control over matrix mechanics and biochemistry. An engineered protein hydrogel system was then used to determine optimal matrix properties for expansion of neural progenitor cells (NPCs). A family of hydrogels with varied matrix stiffness, proteolytic degradability, and adhesive ligand concentration was screened for conditions that maintained NPC stem cell function, or "stemness." Strikingly, stemness maintenance was only correlated with matrix degradability. Matrix degradation and remodeling was required for cadherin-mediated cell-cell contact, which in turn modulated stemness through activation of β-catenin signaling. These results were validated in two other hydrogel systems capable of chemical and physical matrix remodeling. Finally, the dissertation ends with a study exploring the interplay among cell-matrix interactions, cell-cell contact, and soluble factor signaling in a model of peripheral nerve injury. Collectively, the results presented herein demonstrate the power of carefully controlled ECM mimics to identify key regulators of cellular behavior.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2017 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Madl, Christopher M |
|---|---|
| Associated with | Stanford University, Department of Bioengineering. |
| Primary advisor | Heilshorn, Sarah |
| Thesis advisor | Heilshorn, Sarah |
| Thesis advisor | Plant, Giles |
| Thesis advisor | Yang, Fan, (Bioengineering researcher and teacher) |
| Advisor | Plant, Giles |
| Advisor | Yang, Fan, (Bioengineering researcher and teacher) |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Christopher M. Madl. |
|---|---|
| Note | Submitted to the Department of Bioengineering. |
| Thesis | Thesis (Ph.D.)--Stanford University, 2017. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2017 by Christopher Matthew Madl
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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