Peptide Amphiphile (PA) molecules developed in the author's laboratory and others have shown great versatility in creating self-assembled nanostructures with built-in biological and/or chemical functionalities. Their applications in spinal cord injury repair, angiogenesis, promoting cell adhesion and templating inorganic materials have also been well studied. Complementing previous compositional studies, where functions are mostly acquired via changes in compositions, this work has investigated strategies and methods to introduce architectural information into PA systems. Contributions of this work focused on understanding how temperature, pH, screening ions, aging, steric effects, and molecular design affect the formation of self-assembled nanostructures and downstream performance of macroscopic materials. A thermal energy pathway for self-assembly was discovered which drastically changes the final macroscopic nature of the material. In particular, it was observed that when a PA solution is heated to 80°C for 30 minutes aggregate of PA molecules formed a two-dimensional plaque structure at the elevated temperature. Upon cooling the plaque structure breaks into highly aligned fibrils to form a liquid crystalline substance as demonstrated by birefringence. By manually dragging this liquid crystalline substance from a pipette onto salty media, it is possible to extend and fix the alignment over arbitrary lengths creating noodle-shaped viscoelastic strings. In great contrast, simple aging of PA solution at room temperature cannot lead to such drastic changes in short amount of time. It is hypothesized this emergent plaque structures are formed through aggregation of dehydrated fibers at elevated temperature. Besides temperature, pH value, screening ions and steric effects were also found to actively participate in this process. High repulsive interactions due to electrostatics and bulkiness of molecules inhibit the formation of liquid crystalline substance through heat treatment. By reducing potential interfiber ionic bridging through pH adjustment and molecular design, hydrogel fluidity can be increased and leads to improved robustness of final materials. Preferential cellular orientation and outgrowth of mammalian cells were achieved using such newly developed extracellular matrix (ECM) analogues in living systems. We envision these PA strings as substrates for "cellular wires" to direct biological function in space or as templates for alignment of one-dimensional nanostructures over macroscopic distances without the use of lithography.
Finally, this work also investigated strategies and methods to create and analyze combinatorial hydrogel arrays with encapsulated cells using a high throughput system. In these efforts, combinations of different PA molecules could be mixed at various ratios with cells into hydrogel arrays by automatic fluid handling robots. It is proved that with a small amount of cells, RNA can be quickly isolated and analyzed by one-step multiplex reverse-transcriptase polymerase chain reaction (RT-PCR). Using this system, culture conditions can be changed to test multiple variables, such as PA concentration, growth factors, media type etc. While the system still needs optimization, it could potentially facilitate our efforts for discovering material candidates to be used in biomedical applications.
|Advisor:||Stupp, Samuel I.|
|Commitee:||Messersmith, Phillip, Shea, Lonnie, Shull, Kenneth|
|Department:||Materials Science and Engineering|
|School Location:||United States -- Illinois|
|Source:||DAI-B 69/12, Dissertation Abstracts International|
|Keywords:||Alignment, Biomaterials, Liquid crystals, Peptide amphiphiles|
Copyright in each Dissertation and Thesis is retained by the author. All Rights Reserved
The supplemental file or files you are about to download were provided to ProQuest by the author as part of a
dissertation or thesis. The supplemental files are provided "AS IS" without warranty. ProQuest is not responsible for the
content, format or impact on the supplemental file(s) on our system. in some cases, the file type may be unknown or
may be a .exe file. We recommend caution as you open such files.
Copyright of the original materials contained in the supplemental file is retained by the author and your access to the
supplemental files is subject to the ProQuest Terms and Conditions of use.
Depending on the size of the file(s) you are downloading, the system may take some time to download them. Please be