Molecular Insights into Amyloid Oligomers and Their Interactions

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UIC Department of Chemical Engineering Seminar
Tuesday January 31th, 2012
11:00 AM
CEB 218
Jie Zheng
University of Akron
Department of Chemical and Biomolecular Engineering
Molecular Insights into Amyloid Oligomers and
Their Interactions with Model Membranes
Abstract
The aggregation of monomeric proteins/peptides to form ordered amyloid oligomers/fibrils is a
pathogenic hallmark of many degenerative diseases including Alzheimer's, Parkinson's, and
prion diseases. Despite of significant progress, oligomeric structures and associated toxicity at
the very early stage of aggregation remain unclear. Structural knowledge of these oligomers is
essential for understanding the pathology of amyloidoses and for the rational design of drugs
against amyloid diseases. This talk will cover our recent works in three aspects.
(i) We identify a series of atomic structures of amyloid oligomers with different sequences (Aβ,
hIAPP, GNNQQNY, and K3) and structural morphologies (micelles, annulars, triangulars,
globulomers, and linears), delineate several common features in amyloid structures, and
illustrate aggregation driving forces that stabilize these oligomeric structures.
(ii) More importantly, we further examine the interactions of amyloid oligomers with lipid
bilayers to examine membrane-damage mechanisms by varying oligomeric morphology,
lipid compositions, cholesterol contents, and position and orientation of Aβ relative to lipid
bilayers. Two postulated mechanisms of membrane damage (membrane thinning vs. ion
channel) associated with amyloid toxicity are discussed.
(iii)In addition, due to the complex nature of cell membranes, we also alternatively employ selfassembled monolayers (SAMs) as model systems to study the aggregation and
conformational changes of Aβ peptides using an integrated simulation and experimental
approach. The complementary results from simulations and experiments reveal different Aβ
adsorption, structural transition, and aggregation scenarios on the SAMs, providing parallel
insights into the understanding of Aβ structure and aggregation on cell membrane.
The seminar is held in CEB (Chemical Engineering Building)
Room 218 at 810 S. Clinton Street, Chicago, IL 60607.
Reception will start at 10:45 am.