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Collective behavior in two-dimension...

Guo, Chinlin.

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Collective behavior in two-dimensional biological systems: Receptor clustering and beta-sheet aggregation.

紀錄類型:	書目-語言資料,印刷品 : Monograph/item
正題名/作者:	Collective behavior in two-dimensional biological systems: Receptor clustering and beta-sheet aggregation./
作者:	Guo, Chinlin.
面頁冊數:	86 p.
附註:	Chairperson: Herbert Levine.
Contained By:	Dissertation Abstracts International62-09B.
標題:	Biophysics, General. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3025945
ISBN:	0493381686

Collective behavior in two-dimensional biological systems: Receptor clustering and beta-sheet aggregation.
Guo, Chinlin.

Collective behavior in two-dimensional biological systems: Receptor clustering and beta-sheet aggregation. - 86 p.

Chairperson: Herbert Levine.

Thesis (Ph.D.)--University of California, San Diego, 2001.

We studied two particular biomedical systems which exhibit collective molecular behavior. One is clustering of tumor necrosis factor receptor I (TNFR1), and another is β-sheet folding and aggregation. Receptor clustering has been shown to be a crucial step in many signaling events but its biological meaning has not been adequately addressed. Here, via a simple lattice model, we show how cells use this clustering machinery to enhance sensitivity as well as robustness. On the other hand, intracellular deposition of aggregated protein rich in β-sheet is a prominent cytopathological feature of most neurodegenerative diseases. How this aggregation occurs and how it responds to therapy is not completely understood. Here, we started from a reconstruction of the H-bond potential and carry out a full investigation of β-sheet thermodynamics as well as kinetics. We show that β-sheet aggregation is most likely due to molecular stacking and found that the minimal length of an aggregate mutant polymer corresponds well with the number observed in adult Huntington's disease. We have also shown that molecular agents such as dendrimers might fail at high-dose therapy; instead, a potential therapy strategy is to block β-turn formation. Our predictions can be used for future experimental tests and clinical trials.

ISBN: 0493381686Subjects--Topical Terms:

1019105
Biophysics, General.

Collective behavior in two-dimensional biological systems: Receptor clustering and beta-sheet aggregation.
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520 $a We studied two particular biomedical systems which exhibit collective molecular behavior. One is clustering of tumor necrosis factor receptor I (TNFR1), and another is β-sheet folding and aggregation. Receptor clustering has been shown to be a crucial step in many signaling events but its biological meaning has not been adequately addressed. Here, via a simple lattice model, we show how cells use this clustering machinery to enhance sensitivity as well as robustness. On the other hand, intracellular deposition of aggregated protein rich in β-sheet is a prominent cytopathological feature of most neurodegenerative diseases. How this aggregation occurs and how it responds to therapy is not completely understood. Here, we started from a reconstruction of the H-bond potential and carry out a full investigation of β-sheet thermodynamics as well as kinetics. We show that β-sheet aggregation is most likely due to molecular stacking and found that the minimal length of an aggregate mutant polymer corresponds well with the number observed in adult Huntington's disease. We have also shown that molecular agents such as dendrimers might fail at high-dose therapy; instead, a potential therapy strategy is to block β-turn formation. Our predictions can be used for future experimental tests and clinical trials.
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