Nanoscale membrane structure : from lateral organization to proton permeability
Abstract/Contents
- Abstract
- Membranes composed of lipids and proteins are universal features of living organisms. These layers that are only a few nanometers thick differentiate between life and death for cells. Despite the importance of biological membranes in compartmentalizing cellular space and separating the cell from its surroundings, many aspects of membrane structure and functional organization remain a mystery. The plasma membrane of mammalian cells contains thousands of different membrane proteins and thousands of different lipid species, and the absolute and relative amounts of these components are tightly regulated. Given this dizzying molecular complexity, how these molecules are functionally organized to optimize biochemical processes that occur at the membrane remains poorly understood. In addition to this complexity, non-mammalian cells contain structurally exotic lipids, whose physical properties and functions in their membranes remain unexplored. This thesis describes my work on elucidating the structure and biophysics of lipid membranes and the functional consequences of membrane structure. I have applied biophysical characterization techniques, imaging mass spectrometry, and chemical synthesis to address these questions. I take a reductionist approach and utilize model membranes and single cell analysis to unravel the complexities of biological systems. I will first describe the development of new methods for using nanoscale secondary ion mass spectrometry (NanoSIMS) to measure the distance between isotopically labeled molecules in lipid bilayers. I take advantage of a process called atomic recombination, in which atoms in sample from different molecules rearrange to form secondary ions when bombarded by a high energy ion beam. This process depends on the distance between the molecules and can therefore be used to measure the distance between the molecules. After benchmarking this new method, I use it to show that there are nanoscale lipid clusters in bilayers that had previously been observed indirectly or not at all. I then describe recent results from the structurally unique ladderane lipids, which are exclusively found in bacteria that perform anaerobic ammonium oxidation (anammox). The biological role of these lipids and biophysics of membranes containing them are unknown due to a lack of pure lipids. We approach this problem by synthesizing the natural lipids and unnatural analogs and performing structure-function studies. These experiments reveal an anomalously low proton permeability for ladderane bilayers, suggesting a role for ladderane lipids in preventing the breakdown of transmembrane proton gradients. We further explore the structure-function relationships between lipid molecular structure and resulting lipid bilayer structure.
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 | 2018; ©2018 |
| Publication date | 2018; 2018 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Moss, Frank Russell III |
|---|---|
| Degree supervisor | Boxer, Steven G. (Steven George), 1947- |
| Thesis advisor | Boxer, Steven G. (Steven George), 1947- |
| Thesis advisor | Burns, Noah |
| Thesis advisor | Cegelski, Lynette |
| Degree committee member | Burns, Noah |
| Degree committee member | Cegelski, Lynette |
| Associated with | Stanford University, Department of Chemistry. |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Frank Russell Moss III. |
|---|---|
| Note | Submitted to the Department of Chemistry. |
| Thesis | Thesis Ph.D. Stanford University 2018. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2018 by Frank Russell Moss
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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