Human Plasma Protein Corona on Nanostructured Diatom Biosilica: Elucidating Formation Dynamics and Proteomic Profiles

Upon blood contact, biomaterials rapidly adsorb plasma proteins, forming a protein corona that dictates their biological identities and interactions. While diatom biosilica presents a naturally derived, nanostructured platform for biomaterial applications, its interaction with human plasma at the biomolecular level remains unknown. Here, we investigate the formation dynamics and proteomic composition of the protein corona on diatom biosilica. At the initial stages, we compared two tropical marine diatom species: <i>Cyclotella striata</i> TBI (centric) and <i>Navicula salinicola</i> NLA (pennate). Starting with human serum albumin (HSA) as a model protein and then transitioning to human plasma, we demonstrated that <i>N. salinicola</i> biosilica exhibited a higher capacity for protein adsorption, likely due to its elongated morphology and larger pores. Adsorption occurred immediately and followed pseudo-first-order kinetics, reaching equilibrium within ∼20 min, with HSA predominantly localizing on the biosilica outer surface, based on tomographic confocal imaging. LC-HRMS proteomic analysis revealed that plasma interactions with biosilica induced HSA depletion and selective enrichment of immunoglobulins, homeostatic proteins, and apolipoproteins in the corona. Analyses of protein parameters (i.e., pI and GRAVY values) for the enriched proteins indicate a stronger affinity of biosilica toward hydrophilic and positively charged plasma proteins. Functional annotation of the enriched proteins suggests that biosilica might play a role in immune activity modulation, complement activation, iron homeostasis, as well as the regulation of coagulation and wound healing. These findings unveiled fundamental biomolecular insights governing biosilica-protein interactions, paving the way toward the integration of diatom biosilica into biomaterial engineering, diagnostics, and therapeutic applications.