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Vesicle Tubulation with Self-Assembl...

Grome, Michael William.

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Vesicle Tubulation with Self-Assembling DNA Nanosprings: Biomimetic Nanotechnology Toward the Re-capitulation and Re-Purposing of Sub-cellular Functions within an Artificial Framework.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Vesicle Tubulation with Self-Assembling DNA Nanosprings: Biomimetic Nanotechnology Toward the Re-capitulation and Re-Purposing of Sub-cellular Functions within an Artificial Framework./
Author:	Grome, Michael William.
Published:	Ann Arbor : ProQuest Dissertations & Theses, : 2019,
Description:	147 p.
Notes:	Source: Dissertations Abstracts International, Volume: 81-03, Section: B.
Contained By:	Dissertations Abstracts International81-03B.
Subject:	Nanotechnology. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=13809317
ISBN:	9781085777391

Vesicle Tubulation with Self-Assembling DNA Nanosprings: Biomimetic Nanotechnology Toward the Re-capitulation and Re-Purposing of Sub-cellular Functions within an Artificial Framework.
Grome, Michael William.

Vesicle Tubulation with Self-Assembling DNA Nanosprings: Biomimetic Nanotechnology Toward the Re-capitulation and Re-Purposing of Sub-cellular Functions within an Artificial Framework. - Ann Arbor : ProQuest Dissertations & Theses, 2019 - 147 p.

Source: Dissertations Abstracts International, Volume: 81-03, Section: B.

Thesis (Ph.D.)--Yale University, 2019.

This item must not be sold to any third party vendors.

Natural systems are fraught with complex interactions and dynamic structures that produce the varied functionalities inherent and vital to cellular lifeforms. Despite an existing world of nano-scale functional machines within our bodies, we are yet able to reliably reproduce these systems with sufficient understanding and control of physical properties to tune or re-purpose their functionalities for alternative applications. Through the employment of well understood and highly programmable nucleic acid structural properties and chemistries, we can construct 3-dimensionally complex higher order structures on the nanoscale, using DNA as the building material. Due to the inherent programmability of these DNA "nano-structures", endowed by nucleotide sequence design, the field of structural DNA nanotechnology offers the ability to recapitulate the forms and functions of natural systems under tunable and predictable artificial frameworks. Under the guidance of Dr. Chenxiang Lin and by employing basal structural designs by Dr. Zhao Zhang, I have created artificial, structurally and functionally analogous DNA nanostructure biological mimics of natural membrane binding and deforming protein complexes, such as BAR, ESCRT, and Dynamin. Our design, the DNA curl, is a structurally curved monomeric DNA nanostructure capable of polymerizing into nanospring filaments. When labeled with DNA-conjugated amphipathic, membrane-inserting peptides, curls are able to bind vesicle surfaces in a structural stiffness and peptide-labeling density-dependent manner. Upon binding, spherical vesicles of cellular and subcellular sizes are ultimately deformed into tubules. These result from either high membrane surface coverage inducing membrane asymmetry and spontaneous tubulation, or via the polymerization of curls into nanosprings mediated by the addition of linker strands. The modularity and tunability of this system is exhibited through structural variants in curl stiffness, number of peptide labels, presence or absence of polymerization agents, as well as variations in resource and environmental conditions. All of these variables are able to be systematically modified to predictably and precisely determine outcomes in tubulation efficiencies, tubule structures, and population diversity/homogeneity. While this system is roughly functionally biomimetic, the exact mechanisms of action are not fully realized. Ultimately, mechanistic hypotheses are presented to provide context to system functionality so that alterations in designs can be made for future applications and re-purposing of the curl's form and function. Just as a robotic arm is but one step toward an automated factory, nano-structural designs are stepping stones toward entirely artificial subcellular systems that may provide new insight into the complex functions of our natural systems as well as mechanical frameworks for future applications in drug delivery, artificial cells, and augmented life.

ISBN: 9781085777391Subjects--Topical Terms:

526235
Nanotechnology.
Subjects--Index Terms:

Biomimicry

Vesicle Tubulation with Self-Assembling DNA Nanosprings: Biomimetic Nanotechnology Toward the Re-capitulation and Re-Purposing of Sub-cellular Functions within an Artificial Framework.
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520 $a Natural systems are fraught with complex interactions and dynamic structures that produce the varied functionalities inherent and vital to cellular lifeforms. Despite an existing world of nano-scale functional machines within our bodies, we are yet able to reliably reproduce these systems with sufficient understanding and control of physical properties to tune or re-purpose their functionalities for alternative applications. Through the employment of well understood and highly programmable nucleic acid structural properties and chemistries, we can construct 3-dimensionally complex higher order structures on the nanoscale, using DNA as the building material. Due to the inherent programmability of these DNA "nano-structures", endowed by nucleotide sequence design, the field of structural DNA nanotechnology offers the ability to recapitulate the forms and functions of natural systems under tunable and predictable artificial frameworks. Under the guidance of Dr. Chenxiang Lin and by employing basal structural designs by Dr. Zhao Zhang, I have created artificial, structurally and functionally analogous DNA nanostructure biological mimics of natural membrane binding and deforming protein complexes, such as BAR, ESCRT, and Dynamin. Our design, the DNA curl, is a structurally curved monomeric DNA nanostructure capable of polymerizing into nanospring filaments. When labeled with DNA-conjugated amphipathic, membrane-inserting peptides, curls are able to bind vesicle surfaces in a structural stiffness and peptide-labeling density-dependent manner. Upon binding, spherical vesicles of cellular and subcellular sizes are ultimately deformed into tubules. These result from either high membrane surface coverage inducing membrane asymmetry and spontaneous tubulation, or via the polymerization of curls into nanosprings mediated by the addition of linker strands. The modularity and tunability of this system is exhibited through structural variants in curl stiffness, number of peptide labels, presence or absence of polymerization agents, as well as variations in resource and environmental conditions. All of these variables are able to be systematically modified to predictably and precisely determine outcomes in tubulation efficiencies, tubule structures, and population diversity/homogeneity. While this system is roughly functionally biomimetic, the exact mechanisms of action are not fully realized. Ultimately, mechanistic hypotheses are presented to provide context to system functionality so that alterations in designs can be made for future applications and re-purposing of the curl's form and function. Just as a robotic arm is but one step toward an automated factory, nano-structural designs are stepping stones toward entirely artificial subcellular systems that may provide new insight into the complex functions of our natural systems as well as mechanical frameworks for future applications in drug delivery, artificial cells, and augmented life.
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