Microfluidic and optofluidic investigation of biological macromolecule phase transistions
Abstract/Contents
- Abstract
- Phase transitions are ubiquitous in nature. Fundamental study of phase transition phenomena is a cornerstone of condensed matter physics, and theoretical results in this area guide technology development in material science. Phase transitions also play an important role in biology. Biological macromolecule phase transitions occur in many biological processes, for example the gel-liquid transition in lipid bilayers and amyloid formation in protein aggregation disease. From a technological standpoint, the ability to crystallize proteins has enabled one of the most important advances in biology of the last century: protein structure determination with X-ray crystallography. However, biological macromolecule phase transitions often display stark phenomenological differences from their inorganic analogs. This owes to the sheer size and complexity of proteins and nucleic acid complexes. Macromolecular phase transition theory is rich in subtleties, anecdotal & counter-intuitive results, and often diverges from predictions of classical theory. In addition to developing theory, fundamental study in this area is also critical for improvements in high-throughput crystallography efforts and in understanding mechanisms of devastating neurodegenerative diseases. This thesis approaches the study of macromolecule phase transitions through the development of new measurement technology. In this work, spectroscopic and imaging techniques are combined with microfluidic systems to provide insight into three areas of macromolecule phase transitions. First, dynamic light scattering and microscopy are integrated onto a microfluidic platform to study and optimize protein crystallization. Additionally dynamic light scattering is combined with fluorescence spectroscopy to investigate amyloid fibril aggregation. Finally, a new technology is presented that demonstrates high-throughput mapping of macromolecule structure by integrating single-molecule fluorescence resonance energy transfer spectroscopy with a microfluidic mixing platform. This lab-on-a-chip platform enables examination of conformational transitions in nucleic acids in response to changes in the chemical and molecular environment in order to create a conformational "phase diagram". In addition to presenting new insight into the mechanism of protein crystallization and protein aggregation, this thesis introduces new technologies for studying biological macromolecule phase transitions.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2012 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Streets, Aaron Michael |
|---|---|
| Associated with | Stanford University, Department of Applied Physics |
| Primary advisor | Quake, Stephen Ronald |
| Thesis advisor | Quake, Stephen Ronald |
| Thesis advisor | Doniach, S |
| Thesis advisor | Kopito, Ron Rieger |
| Advisor | Doniach, S |
| Advisor | Kopito, Ron Rieger |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Aaron Michael Streets. |
|---|---|
| Note | Submitted to the Department of Applied Physics. |
| Thesis | Thesis (Ph.D.)--Stanford University, 2012. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2012 by Aaron Michael Streets
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
Also listed in
Loading usage metrics...