A new pair of glasses for looking at protein-surfactant interactions
23 September 2020, 12:57
Systems that contain both proteins and surfactants are ubiquitous in daily products, from efficient detergents and cosmetic products to life-saving therapeutic formulations. Surfactants are amphiphilic molecules composed of both water-loving and water-hating moieties. They are routinely added to liquid pharmaceutical formulations to enhance the stability of the drug, but these can also trig the degradation of the protein. Although protein-surfactant systems have been studied for decades, a general mechanistic understanding is still missing, and their inherent complexity requires novel approaches to further investigate these systems.
The core work of our recent investigations has been performed in close collaboration between the Pharmaceutical Development research group at Lund University with our industrial partners SARomics Biostructures, Ferring Pharmaceuticals and Enza Biotech, and researchers at scattering research infrastructures Institute Laue-Langevin, ISIS Spallation Source and European Spallation Source.
In our latest study, published in the journal Nanoscale Advances, we have stablished a multi-technique approach to investigate these systems, where we combine in house calorimetry and spectroscopy methods with advanced characterisation methods at nuclear magnetic resonance and neutron scattering research facilities. The studies of a model system comprised of human growth hormone, a therapeutic protein, and sodium dodecylsulfate, a surfactant widely used in cosmetic products, showed different interaction stages between these. Mainly, the results demonstrate that the protein remains colloidally stable, but the native conformation is lost in the presence of surfactant, and the structural, dynamic and conformational landscape of the protein is directly determined. Importantly, this holistic approach connected the results from the different techniques and enabled the molecular mechanism behind changes at the nanoscopic scale to be discerned.
The studies performed by our research group establish a novel methodology for integrative exploration of protein stability and function. The implementation of this methodology to formulated drugs will provide detailed information on the interaction between proteins and excipients. Future investigations will provide a better knowledge of the interactions between proteins and surfactant, where the rational design of products will take the main role in the development of better-formulated drugs.