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Thermodynamic Evidence That Ganglioside-Mediated Insertion Of Botulinum A Into The Cholinergic Nerve Ending May Precede Endocytosis And Acidification: A Langmuir Film Study

Botulinum Neurotoxin (BoNT) is one of the most potent toxins known to human kind. The Atomic Force Microscope (AFM) was employed to investigate the conditions under which BoNT type A heavy chain would bind and/or insert into mica supported dipalmitoylphosphatidylcholine (DPPC) lipid bilayers. As an alternate technique, DPPC/GT1b or total ganglioside extract (80:20) monolayers of a Langmuir Blodgett (LB) Trough were adapted to be artificial membrane models for toxin insertion studies. We conclude that LB monolayer studies are a promising candidate for BoNT/A membrane insertion investigation. Botulinum neurotoxin serotype A insertions into the LB monolayers in the presence of BoNT/A low affinity ganglioside receptor alone, independent of pH. This thermodynamic evidence indicates that BoNT/A may begin its heavy chain insertion into the cholinergic nerve ending before endocytosis and acidification.

Identiferoai:union.ndltd.org:BGMYU2/oai:scholarsarchive.byu.edu:etd-2272
Date14 December 2007
CreatorsStrongin, Bradley Adam
PublisherBYU ScholarsArchive
Source SetsBrigham Young University
Detected LanguageEnglish
Typetext
Formatapplication/pdf
SourceTheses and Dissertations
Rightshttp://lib.byu.edu/about/copyright/

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