Müller, Christian Thomas Benedikt. The interaction of amyloid-β peptide with lipid membranes and glycosaminoglycans. 2012, PhD Thesis, University of Basel, Faculty of Science.
Official URL: http://edoc.unibas.ch/diss/DissB_10083
In order to elucidate the role of GAGs in the Aβ(1-40) fibrillization process, we investigate the interaction of Aβ(1-40) with heparin. First, CD measurements demonstrate the effect of physico-chemical parameters, including pH, ionic strength and temperature, on the conformational state of Aβ(1-40). These measurements lead to experimental conditions, in which the interaction of monomeric Aβ(1-40) with heparin can be studied. The monomeric state of Aβ(1-40) is a prerequisite for a full thermodynamic characterization of the interaction by ITC. Under the given conditions, ITC experiments demonstrate that Aβ(1-40) interacts
with high affinity with heparin. CD spectroscopy reveals a structural transition of Aβ(1-40) from random-coil to β-structure. By studying the double-d isomers of Aβ(1-40), we identify a molecular pattern of the Aβ(1-40)-heparin interaction. We predict the binding constant for the Aβ(1-40)-heparin interaction at physiological ionic strength by using the oligolysine model. Finally, CD measurements reveal that GAGs do not induce a structural transition of Aβ(1-40) at physiological pH.
In the last part of the thesis, the interaction of Aβ(1-40) to cationic lipid vesicles is studied. CD spectroscopy measurements demonstrate that Aβ(1-40) undergoes two sequential structural transitions upon the binding to cationic membranes. First, a random-coil to β-structure transition is observed, followed by a transition to an α-helix at high lipid-to-peptide molar ratios. Compared to anionic lipid vesicles, the membrane-induced β-structure of Aβ(1-40) is less pronounced for cationic membranes, mainly due to the higher pH value at the membrane surface. The thermodynamics of the Aβ(1-40) membrane binding is studied with ITC for three buffer conditions, namely Tris-HCl, Mops and Hepes. Dynamic light scattering measurements show that the binding of Aβ(1-40) induces the formation of large
|Committee Members:||Huwyler, Jörg|
|Faculties and Departments:||05 Faculty of Science > Departement Biozentrum > Former Organization Units Biozentrum > Biophysical Chemistry (Seelig J)|
|Bibsysno:||Link to catalogue|
|Number of Pages:||165 S.|
|Last Modified:||30 Jun 2016 10:50|
|Deposited On:||23 Oct 2012 13:41|
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