Regensburg 2013 – scientific programme
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BP: Fachverband Biologische Physik
BP 28: Focus session: Intracellular Spectroscopy
BP 28.8: Talk
Thursday, March 14, 2013, 12:00–12:15, H44
Inhibition of amyloid formation is impeded at the phospholipid interface — •Michael Schleeger1, Corianne vanden Akker2, Maarten Engel2, Tobias Weidner1, Gijsje Koenderinke2, and Mischa Bonn1 — 1Max Planck Institute for Polymer Research, Ackermannweg 10, 55128, Mainz, Germany — 2FOM Institute AMOLF, Science Park 104, 1098 XG Amsterdam, The Netherlands
Several severe human diseases (including Alzheimer's, Parkinson's disease and type 2 diabetes mellitus) are characterized by the deposition of proteins as insoluble fibrils, also called amyloids. Amyloids fibrils are formed by self-assembly of peptide or protein precursors, which aggregate spontaneously into highly well-defined polymeric structures. The formation of amyloids can be inhibited by polyphenols, as has been previously shown in bulk studies. However, recent studies have shown that amyloid fibrils assemble and exert their cytotoxicity at cellular membranes, rather than in bulk solution. We therefore investigated the inhibitor activity specifically at the phospholipid membrane interface. We show, using surface-specific sum frequency generation (SFG) spectroscopy, that the commonly used amyloid inhibitor epigallocatechin gallate (EGCG) is a much less efficient inhibitor of amyloid formation at a lipid interface than in bulk solution. Moreover, we demonstrate that EGCG is not able to disaggregate existing amyloid fibrils at a lipid interface, in contrast to its behavior in bulk. Clearly, inhibitors are much less effective at membrane surfaces, which should be considered during the design and testing of novel amyloid inhibitors.