19 February 2018 Photoacoustic assay for probing amyloid formation: feasibility study
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Abstract
The formation of amyloid – aggregate of misfolded proteins – is associated with more than 50 human pathologies, including Alzheimer’s disease, Parkinson’s disease, and Type 2 diabetes mellitus. Investigating protein aggregation is a critical step in drug discovery and development of therapeutics targeted to these pathologies. However, screens to identify protein aggregates are challenging due to the stochastic character of aggregate nucleation. Here we employ photoacoustics (PA) to screen thermodynamic conditions and solution components leading to formation of protein aggregates. Particularly, we study the temperature dependence of the Gruneisen parameter in optically-contrasted, undersaturated and supersaturated solutions of glycoside hydrolase (lysozyme). As nucleation of protein aggregates proceeds in two steps, where the first is liquid-liquid separation (rearrangement of solute’s density), the PA response from complex solutions and its temperature-dependence monitor nucleation and differentiate undersaturated and supersaturated protein solutions. We demonstrate that in the temperature range from 22 to 0° C the PA response of contrasted undersaturated protein solution behaves similar to water and exhibits zero thermal expansion at 4°C or below, while the response of contrasted supersaturated protein solution is nearly temperature independent, similar to the behavior of oils. These results can be used to develop a PA assay for high-throughput screening of multi-parametric conditions (pH, ionic strength, chaperone, etc.) for protein aggregation that can become a key tool in drug discovery, targeting aggregate formation for a variety of amyloids.
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Elena Petrova, Elena Petrova, Soon Joon Yoon, Soon Joon Yoon, Ivan Pelivanov, Ivan Pelivanov, Matthew O'Donnell, Matthew O'Donnell, } "Photoacoustic assay for probing amyloid formation: feasibility study", Proc. SPIE 10494, Photons Plus Ultrasound: Imaging and Sensing 2018, 1049464 (19 February 2018); doi: 10.1117/12.2290482; https://doi.org/10.1117/12.2290482
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