Interfacial Behaviors of Proteins

Abstract

This chapter will examine the current molecular understanding of proteins confined to solid-liquid, air-water, and oil-water interfaces. Later chapters will address the protein’s response to interfacial stress (Chapters “Evaluation of interfacial stress during drug product development” and “Relating interfacial shear and dilatations stresses to protein aggregation in mAbs”) as well as the quantification of instability (Chapter “Analytical techniques for evaluating protein instability at interfaces”), but this chapter will highlight the tools used to examine the fundamental biophysics of proteins at the interface. The dynamics of a protein at or near an interface differs significantly from the behavior of a protein in a bulk solution phase, but the nature of the unfolding and lateral self-assembly at the interface is not well understood. Moreover, once adsorbed to the surface, the dynamics of the protein are dependent on the particular protein as well as the nature of the surface. This chapter will discuss several analytical tools that have been used to understand protein-protein and protein-surface interactions. Each section of this chapter will provide a brief working principle of the technique followed by some relevant examples to understand the application of these tools to understand protein adsorption. Hypotheses will be presented that correlate the inherent solution-phase stability of the protein with the propensity of the molecule to adsorb and unfold at an interface. Finally, we will discuss the quantitative analysis of multicomponent systems and competitive adsorption. The competitive adsorption will focus on surfactant-protein systems, and we will highlight the role of intermolecular interactions in the dynamics of an adsorbed biomacromolecule.