Engineering Protein Electrophoresis through Surfactant Design

Abstract

Protein separations have important applications in the medical industry. In the absence of physical symptoms, early detection of protein markers for disease can significantly decrease the morbidity and mortality of diseases like cancer, and Alzheimer's. New proteomic approaches are becoming a promising path in the advancement of diagnosis and determination of effective treatments for disease. The specific molecular structure of a denatured protein is a key factor for the development of reliable protein separations. In polyacrylamide gel electrophoresis (PAGE), protein-surfactant interactions play an important role in the identification of proteins. Studies on protein-surfactant complexes have shown that the nature of the binding forces and related interactions originate primarily from the hydrophobic and ionic interactions between proteins and charged surfactants. However, limited information is available to directly correlate the structure of protein-surfactant complexes to their electrophoretic migration. The overall goal of this study is to develop a fundamental structural understanding of protein-surfactant complexes while aiming towards optimizing protein separations. This work focuses on protein denaturation studies using anionic surfactants with different chain architectures. The structural characterization by small angle scattering analysis shows that, based on the architecture of the surfactant, protein-surfactant complexes primarily form pearl-necklace or elongated structures. Working with different surfactant chain structures reveals that probing of structural parameters is essential to the rational improvement of efficiency and resolution in protein electrophoresis. Here, we start to decipher the relationship between surfactant chemistry, macroscopic separation and structural parameters of various protein-surfactant complexes to enable the future design of engineered surfactant formulations.