350113 Effect of Urea on the Surface Activity of Amyloid Beta Peptide

Monday, November 4, 2013
Grand Ballroom B (Hilton)
Melissa Hernandez and Eva Chi, Department of Chemical and Nuclear Engineering, University of New Mexico, Albuquerque, NM

The aggregation of amyloid beta (Aβ40) peptide into insoluble fibrils rich in beta-sheets is a major pathological hallmark of Alzheimer’s disease.  Previously, we showed that Aβ40 is highly surface active and its binding to model lipid membranes seeds fibril formation.  In an effort to better understand the aggregation of Aβ40 in vivo, we studied the surface activity of Aβ40 in the presence of the naturally-occurring osmolyte, urea.  Urea is known to preferentially bind to and increase the solubility of proteins in solution.  We hypothesized that urea will similarly increase the solubility of Aβ40 in solution and thereby decrease the tendency of Aβ40 to adsorb to the air-water interface. To test our hypothesis, we assessed the surface activity of Aβ40 by measuring its adsorption isotherms (surface pressure versus time) in a Langmuir trough with increasing urea concentration in the subphase.  Our results showed that urea lowered the equilibrium adsorption pressure of Aβ40, indicating lower surface activity.  However, the rate of adsorption increased sharply, and the lag time of adsorption was eliminated in the presence of urea.  To better understand our results, we are investigating the roles of some secondary effects, such as pH and ionic strength, on Aβ40 surface activity.  Understanding how Aβ40 behaves in cell-mimicking environments will provide insight as to why and how Aβ40 aggregates into insoluble fibrils in the brain, thereby creating a foundation to begin treating and preventing Alzheimer’s disease.

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