Upconverting nanoparticles as a new class of optical sensors for visualizing mechanical forces in vivo

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Abstract/Contents

Abstract
Mechanical forces influence a variety of biological processes, including stem cell differentiation, muscle contractions, and disease. However, few sensors have the nanoscopic size, signal stability, or dynamic range to measure forces in vivo. In my research, I design lanthanide-based upconverting nanoparticles (UCNPs) that emit visible light when excited with near infrared light, thereby enabling background-free imaging. In the presence of a mechanical stimuli, like a push or a squeeze, they change color, allowing us to see differences in mechanical environments and track force-dependent behavior. These mechanosensitive nanoparticles have broad applications, as they can be deployed in a variety of biological systems with minimal invasiveness through the bloodstream, ingested, or even taken up by the roots of a plant. Further, they represent an entirely new class of probes for monitoring mechanotransduction in biology. First, I will discuss how I achieve bright, sub-50 nm mechanosensitive UCNPs. In one strategy, d-metal ions couple to lanthanide ions with an efficiency that varies with pressure. In another strategy, a core-shell architecture enhances upconversion efficiency, while synthetically induced strain at the core-shell interface tunes sensitivity. By looking at different crystal phases and shell materials, I create a toolkit of optical sensors, all with a reproducible and ratiometric color response to mechanical stimuli. Then, I evaluate the biocompatibility and performance of UCNPs in biological environments, including a range of buffers, pH gradients, and in vivo in C. elegans worms. Finally, I demonstrate the first in vivo visualization of mechanical stresses involved in C. elegans digestion. Real-time videos reveal how stresses change both spatially and temporally, opening up future directions for monitoring disease and its impact on mechanotransduction.

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 2019; ©2019
Publication date 2019; 2019
Issuance monographic
Language English

Creators/Contributors

Author Lay, Alice
Degree supervisor Dionne, Jennifer Anne
Degree supervisor Ganguli, Surya, 1977-
Thesis advisor Dionne, Jennifer Anne
Thesis advisor Ganguli, Surya, 1977-
Thesis advisor Goodman, Miriam Beth
Degree committee member Goodman, Miriam Beth
Associated with Stanford University, Department of Applied Physics.

Subjects

Genre Theses
Genre Text

Bibliographic information

Statement of responsibility Alice Lay.
Note Submitted to the Department of Applied Physics.
Thesis Thesis Ph.D. Stanford University 2019.
Location electronic resource

Access conditions

Copyright
© 2019 by Alice Lay
License
This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).

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