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ForceSensingApplicationsofDNAOrigamiNanodevices_MHudoba.pdf (40.27 MB)
ETD Abstract Container
Abstract Header
Force Sensing Applications of DNA Origami Nanodevices
Author Info
Hudoba, Michael W
Permalink:
http://rave.ohiolink.edu/etdc/view?acc_num=osu1471474143
Abstract Details
Year and Degree
2016, Doctor of Philosophy, Ohio State University, Mechanical Engineering.
Abstract
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.
Committee
Carlos Castro (Advisor)
Michael Poirier (Committee Member)
Soheil Soghrati (Committee Member)
Jonathan Song (Committee Member)
Pages
355 p.
Subject Headings
Mechanical Engineering
;
Nanotechnology
Keywords
DNA origami
;
DNA nanotechnology
;
nanodynamics
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Refworks
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Citations
Hudoba, M. W. (2016).
Force Sensing Applications of DNA Origami Nanodevices
[Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1471474143
APA Style (7th edition)
Hudoba, Michael.
Force Sensing Applications of DNA Origami Nanodevices.
2016. Ohio State University, Doctoral dissertation.
OhioLINK Electronic Theses and Dissertations Center
, http://rave.ohiolink.edu/etdc/view?acc_num=osu1471474143.
MLA Style (8th edition)
Hudoba, Michael. "Force Sensing Applications of DNA Origami Nanodevices." Doctoral dissertation, Ohio State University, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=osu1471474143
Chicago Manual of Style (17th edition)
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Document number:
osu1471474143
Download Count:
178
Copyright Info
© 2016, all rights reserved.
This open access ETD is published by The Ohio State University and OhioLINK.