東華大學圖書館 |

語系: 繁體中文

說明(常見問題)

回圖書館首頁

手機版館藏查詢

登入

回首頁

切換: 標籤 | MARC模式 | ISBD

A Novel Method for Studying Nucleate...

Ting, Christina L.

FindBook

Google Book

Amazon

博客來

A Novel Method for Studying Nucleated Pathways in Membranes: Development and Applications for Gene Delivery.

紀錄類型:	書目-語言資料,印刷品 : Monograph/item
正題名/作者:	A Novel Method for Studying Nucleated Pathways in Membranes: Development and Applications for Gene Delivery./
作者:	Ting, Christina L.
面頁冊數:	118 p.
附註:	Source: Dissertation Abstracts International, Volume: 74-04(E), Section: B.
Contained By:	Dissertation Abstracts International74-04B(E).
標題:	Biophysics, General. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3544631
ISBN:	9781267757586

A Novel Method for Studying Nucleated Pathways in Membranes: Development and Applications for Gene Delivery.
Ting, Christina L.

A Novel Method for Studying Nucleated Pathways in Membranes: Development and Applications for Gene Delivery. - 118 p.

Source: Dissertation Abstracts International, Volume: 74-04(E), Section: B.

Thesis (Ph.D.)--California Institute of Technology, 2013.

The development of a safe, selective, and efficient gene delivery system is key to the success of human gene therapy. In polymer-based gene delivery systems, biocompatible polymers electrostatically bind and condense the genetic material into protective nanoparticles. These nanoparticles must subsequently overcome several challenges, which remain poorly understood. In particular, once internalized by the cell, the nanoparticles are trapped inside a membrane-bound compartment called the endosome. In the proton sponge hypothesis, the buffering capacity of the polymers leads to an increase in osmotic pressure that eventually ruptures the endosomal membrane and releases the trapped nanoparticles.

ISBN: 9781267757586Subjects--Topical Terms:

1019105
Biophysics, General.

A Novel Method for Studying Nucleated Pathways in Membranes: Development and Applications for Gene Delivery.
LDR:03503nam a2200313 4500 001 1964986
005 20141010092949.5
008 150210s2013 ||||||||||||||||| ||eng d
020 $a 9781267757586
035 $a (MiAaPQ)AAI3544631
035 $a AAI3544631
040 $a MiAaPQ $c MiAaPQ
100 1 $a Ting, Christina L. $3 2101554
245 1 2 $a A Novel Method for Studying Nucleated Pathways in Membranes: Development and Applications for Gene Delivery.
300 $a 118 p.
500 $a Source: Dissertation Abstracts International, Volume: 74-04(E), Section: B.
500 $a Adviser: Zhen-Gang Wang.
502 $a Thesis (Ph.D.)--California Institute of Technology, 2013.
520 $a The development of a safe, selective, and efficient gene delivery system is key to the success of human gene therapy. In polymer-based gene delivery systems, biocompatible polymers electrostatically bind and condense the genetic material into protective nanoparticles. These nanoparticles must subsequently overcome several challenges, which remain poorly understood. In particular, once internalized by the cell, the nanoparticles are trapped inside a membrane-bound compartment called the endosome. In the proton sponge hypothesis, the buffering capacity of the polymers leads to an increase in osmotic pressure that eventually ruptures the endosomal membrane and releases the trapped nanoparticles.
520 $a To obtain a mechanistic understanding of the endosomal escape, we first develop a coarse-grained model to study the equilibrium interaction between a positively charged nanoparticle and a lipid membrane. Results indicate the existence of a pore with an inserted particle, whose metastability depends on the membrane tension and particle properties (size and charge). These pores are subsequently shown to lower the critical tension necessary for membrane rupture, thus possibly enhancing the release of the trapped genetic material from the endosome.
520 $a Next, we address the actual escape pathway, which is likely a thermally nucleated process and cannot be simulated directly or studied by equilibrium methods. Hence, we develop a novel method for studying minimum free energy paths in membranes. Our results indicate that thermally nucleated rupture may be an important factor for the low rupture strains observed in lipid membranes. Under the moderate tensions found in this regime, there are multiple pathways for crossing the membrane: (1) particle-assisted membrane rupture, (2) particle insertion into a metastable pore followed by translocation and membrane resealing, and (3) particle insertion into a metastable pore followed by membrane rupture. This suggests a direct role of the nanoparticle in the endosomal escape not previously envisioned in the proton sponge hypothesis, and illustrates the importance of having an induced tension on the membrane.
520 $a Finally, the methodology developed in this work represents the most advanced theoretical technique for describing nucleation pathways in soft condensed matter systems that also include hard-particle degrees of freedom. We expect the method to be useful for studying a wide range of nucleation phenomena beyond membrane systems, for example, in nanoparticle polymer composites.
590 $a School code: 0037.
650 4 $a Biophysics, General. $3 1019105
650 4 $a Engineering, Chemical. $3 1018531
690 $a 0786
690 $a 0542
710 2 $a California Institute of Technology. $b Biochemistry and Molecular Biophysics. $3 2101555
773 0 $t Dissertation Abstracts International $g 74-04B(E).
790 $a 0037
791 $a Ph.D.
792 $a 2013
793 $a English
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3544631