Unraveling how nanoscale curvature drives formation of lysozyme protein monolayers on inorganic oxide surfaces

Abstract The development of nanostructured material interfaces is critical to various application areas spanning diverse fields such as medicine, energy, and sensing. One of the most promising areas involves nanomedicine and drug delivery and involves the formation of noncovalently adsorbed protein coatings on nanostructured surfaces such as inorganic nanoparticles. The coatings can form naturally as part of the so-called protein corona or be purposely incorporated as functional elements to evade immune recognition or to enable enzymatic function, for example. To date, most relevant studies have examined the underlying adsorption processes on planar surfaces while the effect of nanoscale curvature on protein adsorption is still being unraveled across many dimensions. Herein, we investigated the ionic strength-dependent adsorption of antibacterial lysozyme protein onto planar and nanostructured silicon oxide surfaces by employing the quartz crystal microbalance-dissipation and localized surface plasmon resonance sensing techniques. Our findings revealed that lysozyme undergoes greater adsorption-related denaturation and spreading on planar surfaces which led to multilayer formation, while nanoscale curvature effects suppress protein denaturation on nanostructured surfaces leading to monolayer formation. We discuss these findings within the context of protein-surface and protein-protein interactions and how subtle changes in adsorption pathways can drive the formation of distinct macromolecular assemblies. Looking forward, we also discuss how such measurement strategies can enable mechanistic insights into the formation of protein coatings on nanostructured surfaces with broad implications for nano-bio interface science.