Interactions at the silica-peptide interface: the influence of particle size and surface functionality.

The variety of interactions that can occur at the silica/aqueous interface makes silica nanoparticles (SiNPs) attractive materials for technological applications. Despite their importance, interfacial interactions are not fully understood. In this contribution, we investigate the effect of (1) particle size and (2) surface functionalization on the adsorption of small biomolecular binders on SiNPs. Small silica binding peptides with different properties (charge, pI, and amino acid composition) were used as binders, while a range of fully characterized SiNPs of diameters ranging between 28 and 500 nm (pristine silica) and SiNPs of ca. 500 nm functionalized with cationic 3-aminopropyl groups and hydrophobic methyl groups was used as binding substrates. Adsorption and binding affinity were investigated by a fluorimetric assay at pH 7.4. A detailed characterization of the surface chemistry of the particles showed that the extent of surface functionalization on modified silica was well below monolayer coverage [by X-ray photoelectron spectroscopy (XPS), ca. 2 and 18 atomic % for the amino- and methyl-modified surfaces, respectively]. Although peptide binding is generally moderated by the physicochemical characteristics of the adsorbing peptide, the introduction of such a small degree of functionality onto silica particles was sufficient to produce drastic changes in adsorption at the silica/aqueous interface. In addition, an increase in peptide adsorption with an increasing particle size, independent of the nature and properties of the peptide, was observed. This particle size effect is attributed to a shift of the dominant binding mechanism toward electrostatic interactions on larger SiNPs. The data presented demonstrate that particle size and surface functionality are both parameters that can substantially influence (bio)molecule uptake via modulation or selection of specific binding modes at the silica/peptide interface. These results are applicable to the design and development of interfaces with specific adsorption/affinity response for biomedical applications, where uptake is important, such as drug delivery. Further, they provide important insights on how peptide affinity and selection during biopanning can be determined by small changes in surface chemistry of the surface of a target that can, in some instances, be associated with the presence of impurities.