Title page for ETD etd-07132006-173748

Type of Document Dissertation
Author McMasters, Mariah Joan Wooldridge
Author's Email Address mmcmas1@lsu.edu
URN etd-07132006-173748
Title Influence of Surface Chemistry on the Aggregation of Beta Amyloid Peptide
Degree Doctor of Philosophy (Ph.D.)
Department Chemistry
Advisory Committee
Advisor Name Title
Robin L. McCarley Committee Chair
Paul S. Russo Committee Co-Chair
H. Barry Dellinger Committee Member
Robert P. Hammer Committee Member
Michael E. Hellberg Dean's Representative
  • reflection-absorption infrared spectroscopy
  • scanning force microscopy
  • self-assembled monolayer
Date of Defense 2006-06-30
Availability unrestricted
Alzheimer's disease is a progressive neurological ailment affecting 4.5 million aging Americans. The disease is characterized by the presence in the brain of self-assembled fibrils consisting of beta amyloid protein (Aβ). Soluble Aβ protein is present in normal human cerebrospinal fluid, but it is unclear what makes the protein aggregate into insoluble plaques. There is evidence that the Aβ fibril assembly is affected by interactions with biological surfaces, such as neuronal membranes. Here, surfaces consisting of self-assembled alkanethiol monolayers with different end groups were used to test the effect of surface chemistry on the structure and morphology of aggregates formed from the Aβ peptide. Reflection-absorption infrared spectroscopy and scanning force microscopy (SFM) were used to examine the interactions of the protein with the monolayers. It was found that the surfaces have a seeding effect on the Aβ protein in solution and can actually induce aggregation of the Aβ protein over time. The outcomes are important, because the work described here is the first attempt at relating the chemical makeup of supported, model monolayer surfaces and their propensity to interact with Aβ peptide in solution. Patterned surfaces consisting of fouling and non-fouling monolayers were constructed to determine how these different areas would affect the deposition and aggregation of the Aβ protein. It appeared that the Aβ protein adsorbed onto the ethylene glycol even though the ethylene glycol-terminated monolayers alone were previously seen to be non-fouling. This was important because it appears that the fouling monolayer can induce a change in conformation that allows the protein to stick to what are normally non-fouling surfaces.

Mica-supported lipid bilayers consisting of 1-Palmitoyl-2-Oleoyl-sn-Glycero-3-Phosphocholine (POPC) and 1-Oleoyl-2-[12-[(7-nitro-2-1,3-benzoxadiazol-4-yl)amino]dodecanoyl]-sn-Glycero-3-Phosphocholine (NBD-PC) were also used as a simple cell membrane model system. Fluorescence photobleaching recovery and SFM were used to determine the effects of association of the fibrils with the bilayers. It was found that the Aβ peptide affected the fluidity of the lipid bilayers and inserted itself into the lipid bilayer. This experiment was important because it offers information about the insertion of the Aβ peptide into cell membranes that could potentially be toxic to cells.

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