Understanding the Interplay between Self-Assembling Peptides and Solution Ions for Tunable Protein Nanoparticle Formation

Protein-based nanomaterials are gaining importance in biomedical and biosensor applications where tunability of the protein particle size is highly desirable. Rationally designed proteins and peptides offer control over molecular interactions between monomeric protein units to modulate their self-assembly and thus particle formation. Here, using an example enzyme–peptide system produced as a single construct by bacterial expression, we explore how solution conditions affect the formation and size of protein nanoparticles. We found two independent routes to particle formation, one facilitated by charge interactions between protein–peptide and peptide–peptide exemplified by pH change or the presence of NO3– or NH4+ and the second route via metal-ion coordination (e.g., Mg2+) within peptides. We further demonstrate that the two independent factors of pH and Mg2+ ions can be combined to regulate nanoparticle size. Charge interactions between protein–peptide monomers play a key role in either promoting or supp...