東華大學圖書館 |

Language: English

Help

回圖書館首頁

手機版館藏查詢

Back

Switch To: Labeled | MARC Mode | ISBD

Lipid-Nanodiscs Formed by Paramagnet...

Di Mauro, Giacomo Maria.

Linked to FindBook

Google Book

Amazon

博客來

Lipid-Nanodiscs Formed by Paramagnetic Polymers for Fast NMR Data Acquisition.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Lipid-Nanodiscs Formed by Paramagnetic Polymers for Fast NMR Data Acquisition./
Author:	Di Mauro, Giacomo Maria.
Published:	Ann Arbor : ProQuest Dissertations & Theses, : 2021,
Description:	220 p.
Notes:	Source: Dissertations Abstracts International, Volume: 83-01, Section: B.
Contained By:	Dissertations Abstracts International83-01B.
Subject:	Chemistry. -
Online resource:	https://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=28667006
ISBN:	9798516089299

Lipid-Nanodiscs Formed by Paramagnetic Polymers for Fast NMR Data Acquisition.
Di Mauro, Giacomo Maria.

Lipid-Nanodiscs Formed by Paramagnetic Polymers for Fast NMR Data Acquisition. - Ann Arbor : ProQuest Dissertations & Theses, 2021 - 220 p.

Source: Dissertations Abstracts International, Volume: 83-01, Section: B.

Thesis (Ph.D.)--University of Michigan, 2021.

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

Membrane proteins are critical components of any cell, and their malfunction is associated with numerous diseases. For this reason, they represent a primary target for various drugs on the market, but both academic and pharmaceutical research is hindered by the challenges associated with obtaining stable and functioning samples.Artificial lipid membranes are crucial for the investigation of membrane proteins because of their ability to simulate the amphipathic native-like environment of the cell membrane. Recent studies have shown the dramatic advantages of using lipid/nanodiscs as compared to other types of membrane mimetics. While the nanodiscs prepared using scaffold proteins, peptides, and proteins have their advantages and limitations; there is significant interest in synthetic polymers because of the broad scope and feasibilities. Macromolecules such as copolymers of styrene and maleic acid (SMA) interact with lipids forming stable discoidal nanoparticles made of bilayer patches wrapped by the polymeric belt. These copolymers have also been used to extract membrane proteins directly from their native environment and isolate them into nanodiscs without using detergents. Despite the many successes reported in the literature, copolymer-nanodiscs still show several limitations, and new formulations are under development. The Ramamoorthy research group focused on the hydrophilic functionalization of a low molecular-weight SMA copolymer. This approach allowed for the tuning and enhancement of these polymers, particularly in the field of nuclear magnetic resonance (NMR) spectroscopy.NMR is widely employed to study nanodiscs reconstituted membrane proteins but suffers from its intrinsic low sensitivity, which necessitates long data acquisition times. Paramagnetic resonance enhancement is among the strategies that have been used to enhance the sensitivity of NMR by reducing the spin-lattice relaxation or T1, a key parameter in assessing the duration of the required data acquisition. However, PRE requires the introduction of PRE-agents in the sample that could alter the sample's stability and function.This thesis reports a novel PRE-agent that does not involve (i) direct labeling of membrane proteins, (ii) the alteration of the surrounding lipid composition, or (iii) the presence of free metal ions in the sample. Specifically, SMA-EA-DOTA copolymer allows the chelation of paramagnetic ions directly in the copolymer-lipid nanodiscs' outer rim without contaminating the nanodiscs' constituents such as lipids and proteins, enabling T1-reduction. A variety of lanthanide ions are investigated to quantify the PRE effects and for use in nanodiscs-enabled studies on membrane systems.Since nanodiscs-forming copolymers act, de facto, as macromolecular detergents, this thesis also investigates the relationship between the critical micelle concentration (c.m.c.) of a set of SMA-copolymers and their ability to form nanodiscs. It was found that the interaction with phospholipids alters the copolymers' c.m.c. values, and the existence of an equilibrium between the «free» or «micellar» copolymer chains and the «nanodiscs-bound» copolymer chains. Because of this equilibrium, the thesis speculates the possibility of substituting inexpensive copolymers after membrane proteins isolation and purification with paramagnetically-tagged copolymers for magnetic resonance studies. Aside from PRE-NMR, membrane proteins reconstituted in paramagnetically-labeled nanodiscs, such as SMA-EA-DOTA, ST-10, ST-100, and mixed formulations, can be studied using other biophysical techniques including electron paramagnetic resonance and dynamic nuclear polarization NMR.Finally, paramagnetically-tagged copolymer nanodiscs can find new applications outside the biophysical and biochemical fields. For instance, these bioinspired paramagnetic nanoparticles might find applications in the fields of drug delivery and magnetic resonance imaging as macromolecular contrast agents for better diagnosis of solid tumors.

ISBN: 9798516089299Subjects--Topical Terms:

516420
Chemistry.
Subjects--Index Terms:

Polymer nanodiscs SMALP

Lipid-Nanodiscs Formed by Paramagnetic Polymers for Fast NMR Data Acquisition.
LDR:05366nmm a2200397 4500 001 2282108
005 20210927083542.5
008 220723s2021 ||||||||||||||||| ||eng d
020 $a 9798516089299
035 $a (MiAaPQ)AAI28667006
035 $a (MiAaPQ)umichrackham003495
035 $a AAI28667006
040 $a MiAaPQ $c MiAaPQ
100 1 $a Di Mauro, Giacomo Maria. $3 3560862
245 1 0 $a Lipid-Nanodiscs Formed by Paramagnetic Polymers for Fast NMR Data Acquisition.
260 1 $a Ann Arbor : $b ProQuest Dissertations & Theses, $c 2021
300 $a 220 p.
500 $a Source: Dissertations Abstracts International, Volume: 83-01, Section: B.
502 $a Thesis (Ph.D.)--University of Michigan, 2021.
506 $a This item must not be sold to any third party vendors.
506 $a This item must not be added to any third party search indexes.
520 $a Membrane proteins are critical components of any cell, and their malfunction is associated with numerous diseases. For this reason, they represent a primary target for various drugs on the market, but both academic and pharmaceutical research is hindered by the challenges associated with obtaining stable and functioning samples.Artificial lipid membranes are crucial for the investigation of membrane proteins because of their ability to simulate the amphipathic native-like environment of the cell membrane. Recent studies have shown the dramatic advantages of using lipid/nanodiscs as compared to other types of membrane mimetics. While the nanodiscs prepared using scaffold proteins, peptides, and proteins have their advantages and limitations; there is significant interest in synthetic polymers because of the broad scope and feasibilities. Macromolecules such as copolymers of styrene and maleic acid (SMA) interact with lipids forming stable discoidal nanoparticles made of bilayer patches wrapped by the polymeric belt. These copolymers have also been used to extract membrane proteins directly from their native environment and isolate them into nanodiscs without using detergents. Despite the many successes reported in the literature, copolymer-nanodiscs still show several limitations, and new formulations are under development. The Ramamoorthy research group focused on the hydrophilic functionalization of a low molecular-weight SMA copolymer. This approach allowed for the tuning and enhancement of these polymers, particularly in the field of nuclear magnetic resonance (NMR) spectroscopy.NMR is widely employed to study nanodiscs reconstituted membrane proteins but suffers from its intrinsic low sensitivity, which necessitates long data acquisition times. Paramagnetic resonance enhancement is among the strategies that have been used to enhance the sensitivity of NMR by reducing the spin-lattice relaxation or T1, a key parameter in assessing the duration of the required data acquisition. However, PRE requires the introduction of PRE-agents in the sample that could alter the sample's stability and function.This thesis reports a novel PRE-agent that does not involve (i) direct labeling of membrane proteins, (ii) the alteration of the surrounding lipid composition, or (iii) the presence of free metal ions in the sample. Specifically, SMA-EA-DOTA copolymer allows the chelation of paramagnetic ions directly in the copolymer-lipid nanodiscs' outer rim without contaminating the nanodiscs' constituents such as lipids and proteins, enabling T1-reduction. A variety of lanthanide ions are investigated to quantify the PRE effects and for use in nanodiscs-enabled studies on membrane systems.Since nanodiscs-forming copolymers act, de facto, as macromolecular detergents, this thesis also investigates the relationship between the critical micelle concentration (c.m.c.) of a set of SMA-copolymers and their ability to form nanodiscs. It was found that the interaction with phospholipids alters the copolymers' c.m.c. values, and the existence of an equilibrium between the «free» or «micellar» copolymer chains and the «nanodiscs-bound» copolymer chains. Because of this equilibrium, the thesis speculates the possibility of substituting inexpensive copolymers after membrane proteins isolation and purification with paramagnetically-tagged copolymers for magnetic resonance studies. Aside from PRE-NMR, membrane proteins reconstituted in paramagnetically-labeled nanodiscs, such as SMA-EA-DOTA, ST-10, ST-100, and mixed formulations, can be studied using other biophysical techniques including electron paramagnetic resonance and dynamic nuclear polarization NMR.Finally, paramagnetically-tagged copolymer nanodiscs can find new applications outside the biophysical and biochemical fields. For instance, these bioinspired paramagnetic nanoparticles might find applications in the fields of drug delivery and magnetic resonance imaging as macromolecular contrast agents for better diagnosis of solid tumors.
590 $a School code: 0127.
650 4 $a Chemistry. $3 516420
650 4 $a Materials science. $3 543314
650 4 $a Biophysics. $3 518360
653 $a Polymer nanodiscs SMALP
653 $a Membrane mimetics
653 $a Paramagnetic resonance enhancement
653 $a Nuclear magnetic resonance
653 $a Bioinspired nanomaterials
653 $a Membrane proteins
690 $a 0485
690 $a 0786
690 $a 0794
710 2 $a University of Michigan. $b Chemistry. $3 2101148
773 0 $t Dissertations Abstracts International $g 83-01B.
790 $a 0127
791 $a Ph.D.
792 $a 2021
793 $a English
856 4 0 $u https://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=28667006