Membrane curvature-dependent intracellular signaling induced by nanoscale surface topography
Abstract/Contents
- Abstract
- Nanoscale surface topography serves as physical signal that induce behavior changes of cells. Despite the potential applications of nanoscale surface topography for cell engineering, the mechanism of how these topographies induce series of intracellular signaling is still not well studied. In this thesis, we investigate several intracellular signaling induced by nanoscale surface topography. We introduce the idea that plasma membrane curvatures generated by these topographies are the key signal transducers in between the cells and the surface, and apply this theory for applications such as cell detection and capture. Rearrangement of the actin cytoskeleton by nanoscale surface topography is one of the major responses that has been observed in many studies. These topographies, with various materials and shapes, induce the local accumulation of filamentous actin (F-actin) around the individual topographies inside cells. These studies, however, did not provide the molecular mechanism of F-actin reorganization. Here we proved that nanostructure-induced plasma membrane curvatures with diameter less than 400 nm are found to effectively trigger Arp2/3 nucleated actin polymerization by recruiting membrane-curvature-associated proteins. Besides actin polymerization, we also observed that nanoscale topography can induce clathrin-mediated endocytosis (CME), which involves the bending and budding of plasma membrane. We found that CME happened more frequently on the nanostructure-induced membrane curvatures with diameters < 400 nm. These curvatures are also found to preferentially recruit several key CME proteins such as clathrin and dynamin, but not non-CME endocytic proteins, such as caveolin-1. With the knowledge of strong interaction between nanoscale surface topography with cells, we develop a topography-based platform for capturing circulating tumor cells (CTC). Capture of CTCs is important for cancer detection and monitor, but also very challenging due to its extremely low concentration within bloodstream. Here we combine nanopillar substrates with antibody-functionalized supported lipid bilayer to both increase capture efficiency and decrease non-specific cell-nanopillar interaction, respectively. In conclusion, this thesis summarizes our approaches of study how nanoscale surface topography induce specific intracellular signaling by inducing plasma membrane curvatures and showing its potential application.
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 | Lou, Hsin-Ya |
|---|---|
| Degree supervisor | Cui, Bianxiao |
| Thesis advisor | Cui, Bianxiao |
| Thesis advisor | Boxer, Steven G. (Steven George), 1947- |
| Thesis advisor | Cegelski, Lynette |
| Degree committee member | Boxer, Steven G. (Steven George), 1947- |
| Degree committee member | Cegelski, Lynette |
| Associated with | Stanford University, Department of Chemistry. |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Hsin-Ya Lou. |
|---|---|
| Note | Submitted to the Department of Chemistry. |
| Thesis | Thesis Ph.D. Stanford University 2018. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2018 by Hsin-Ya Lou
- 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...