Force Sensing Applications of DNA Origami Nanodevices

Bibliographic Details
Main Author: Hudoba, Michael W.
Language:English
Published: The Ohio State University / OhioLINK 2016
Subjects:
Online Access:http://rave.ohiolink.edu/etdc/view?acc_num=osu1471474143
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spelling ndltd-OhioLink-oai-etd.ohiolink.edu-osu14714741432021-08-03T06:38:29Z Force Sensing Applications of DNA Origami Nanodevices Hudoba, Michael W. Mechanical Engineering Nanotechnology DNA origami DNA nanotechnology nanodynamics Mechanical forces in biological systems vary in both length and magnitude by orders of magnitude making them difficult to probe and characterize with existing experimental methodologies. From molecules to cells, forces can act across length scales of nanometers to microns at magnitudes ranging from picoNewtons to nanoNewtons. Although single-molecule techniques such as optical traps, magnetic tweezers, and atomic force microscopy have improved the resolution and sensitivity of such measurements, inherent drawbacks exist in their capabilities due to the nature of the tools themselves. Specifically, these techniques have limitations in their ability to measure forces in realistic cellular environments and are not amenable to in vivo applications or measurements in mimicked physiological environments. In this thesis, we present a method to develop DNA force-sensing nanodevices with sub-picoNewton resolution capable of measuring forces in realistic cellular environments, with future applications in vivo. We use a design technique known as DNA origami to assemble devices with nanoscale geometric precision through molecular self-assembly via Watson-Crick base pairing. The devices have multiple conformational states, monitored by observing a Forster Resonance Energy Transfer signal that can change under the application of force.We expanded this study by demonstrating the design of responsive structural dynamics in DNA-based nanodevices. While prior studies have relied on external inputs to drive relatively slow dynamics in DNA nanostructures, here we developed DNA nanodevices with thermally driven dynamic function. The device was designed with an ensemble of conformations, and we establish methods to tune the equilibrium distribution of conformations and the rate of switching between states. We also show this nanodynamic behavior is responsive to physical interactions with the environment by measuring molecular crowding forces in the sub-picoNewton range, which are known to play a critical role in regulating molecular interactions and processes. Broadly, this work establishes a foundation for nanodevices with thermally driven dynamics that enable new measurement and control functions.We also examine the effect that forces have on the mechanical properties of DNA origami devices by developing a method to automate mesh generation for Finite Element Analysis. With this approach we are able to determine how defects that arise during assembly affect mechanical strain within structures during force application that can ultimately lead to device failure. 2016 English text The Ohio State University / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=osu1471474143 http://rave.ohiolink.edu/etdc/view?acc_num=osu1471474143 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws.
collection NDLTD
language English
sources NDLTD
topic Mechanical Engineering
Nanotechnology
DNA origami
DNA nanotechnology
nanodynamics
spellingShingle Mechanical Engineering
Nanotechnology
DNA origami
DNA nanotechnology
nanodynamics
Hudoba, Michael W.
Force Sensing Applications of DNA Origami Nanodevices
author Hudoba, Michael W.
author_facet Hudoba, Michael W.
author_sort Hudoba, Michael W.
title Force Sensing Applications of DNA Origami Nanodevices
title_short Force Sensing Applications of DNA Origami Nanodevices
title_full Force Sensing Applications of DNA Origami Nanodevices
title_fullStr Force Sensing Applications of DNA Origami Nanodevices
title_full_unstemmed Force Sensing Applications of DNA Origami Nanodevices
title_sort force sensing applications of dna origami nanodevices
publisher The Ohio State University / OhioLINK
publishDate 2016
url http://rave.ohiolink.edu/etdc/view?acc_num=osu1471474143
work_keys_str_mv AT hudobamichaelw forcesensingapplicationsofdnaorigaminanodevices
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