Silica nanostructures find applications in drug delivery, catalysis, and composites, however, understanding of the surface chemistry, aqueous interfaces, and biomolecule recognition remain difficult using current imaging techniques and spectroscopy. A silica force field is introduced that resolves numerous shortcomings of prior silica force fields over the last thirty years and reduces uncertainties in computed interfacial properties relative to experiment from several 100% to less than 5%. In addition, a silica surface model database is introduced for the full range of variable surface chemistry and pH (Q 2 , Q 3 , Q 4 environments with adjustable degree of ionization) that have shown to determine selective molecular recognition. The force field enables accurate computational predictions of aqueous interfacial properties of all types of silica, which is substantiated by extensive comparisons to experimental measurements. The parameters are integrated into multiple force fields for broad applicability to biomolecules, polymers, and inorganic materials (AMBER, CHARMM, COMPASS, CVFF, PCFF, INTERFACE force field).We also explain mechanistic details of molecular adsorption of water vapor, as well as significant variations in the amount and dissociation depth of superficial cations at silica-water interfaces that correlate with zeta-potential measurements and create a wide range of aqueous environments for adsorption and self-assembly of complex molecules. The systematic analysis of binding conformations and adsorption free energies of distinct peptides to silica surfaces is reported separately in a companion paper. The models aid to understand and design silica nanomaterials in 3D atomic resolution, and are extendable to chemical reactions.

Molecular recognition and interactions at the interface between biomolecules and inorganic materials determine important phenomena such as protein adsorption, cell adhesion to biomaterials, or the selective response of biosensors. Events occurring at the biomolecule-inorganic interface, despite their importance, are still poorly understood, thus limiting control of interfacial properties and response. In this contribution, using well-characterized silica nanoparticles and a series of peptides having heterogeneous physicochemical properties (S1: KLPGWSG, S2: AFILPTG, and S3: LDHSLHS) identified from biopanning against the same particles, we identify the driving forces that govern peptide-silica binding. Binding isotherms obtained by fluorimetric assay under different pH conditions allowed us to demonstrate the impact of binding environment (pH) on adsorption behavior of a given peptide-surface silica nanoparticle. Our experimental data suggest a multistep adsorption mechanism leading to the formation of multilayers on silica, in which the prevailing interactions (i.e., electrostatic or hydrophobic/hydrogen bonding) and their relative contribution to the binding event are governed by the identity of the peptide itself, the substrate's surface functionality (hydrophilic or hydrophobic), and the peptide bulk concentration and solution bulk pH. Our studies show how it is possible to modulate peptide uptake on silica, or in fact on any particle, by changing either the surface properties or, more simply, the binding environment. In addition, the data reveal an intrinsic bias toward positively charged sequences in the elution conditions used in the biopanning protocol with much information about strong binder sequence diversity being lost during panning.

Silica nanostructures are biologically available and find wide applications for drug delivery, catalysts, separation processes, and composites. However, specific adsorption of biomolecules on silica surfaces and control in biomimetic synthesis remain largely unpredictable. In this contribution, the variability and control of peptide adsorption on silica nanoparticle surfaces is explained as a function of pH, particle diameter, and peptide electrostatic charge using molecular dynamics simulations with the CHARMM-INTERFACE force field. Adsorption free energies and specific binding residues are analyzed in molecular detail, providing experimentally elusive, atomic-level information on the complex dynamics of aqueous electric double layers in contact with biological molecules. Tunable contributions to adsorption are described in the context of specific silica surface chemistry, including ion pairing, hydrogen bonds, hydrophobic interactions, and conformation effects. Remarkable agreement is found for computed peptide binding as a function of pH and particle size versus experimental adsorption isotherms and zetapotentials. Representative surface models were built using characterization of the silica surfaces by TEM, SEM, BET, TGA, ζ-potential, and surface titration measurements. The results show that the recently introduced interatomic potentials (Emami et al. Chem. Mater. 2014, 26, 2647 enable computational screening of a limitless number of silica interfaces to predict the binding of drugs, cell receptors, polymers, surfactants, and gases under realistic solution conditions at the scale of 1 to 100 nm. The highly specific binding outcomes underline the significance of the surface chemistry, pH, and topography.3

Metallo-oxide (MO)-based bioinorganic nanocomposites promise unique structures, physicochemical properties, and novel biochemical functionalities, and within the past decade, investment in research on materials such as ZnO, TiO 2 , SiO 2 , and GeO 2 has significantly increased. Besides traditional approaches, the synthesis, shaping, structural patterning, and postprocessing chemical functionalization of the materials surface is inspired by strategies which mimic processes in nature. Would such materials deliver new technologies? Answering this question requires the merging of historical knowledge and current research from different fields of science. Practically, we need an effective defragmentation of the research area. From our perspective, the superficial accounting of material properties, chemistry of the surfaces, and the behavior of biomolecules next to such surfaces is a problem. This is particularly of concern when we wish to bridge between technologies in vitro and biotechnologies in vivo. Further, besides the potential practical technological efficiency and advantages such materials might exhibit, we have to consider the wider long-term implications of material stability and toxicity. In this contribution, we present a critical review of recent advances in the chemistry and engineering of MO-based biocomposites, highlighting the role of interactions at the interface and the techniques by which these can be studied. At the end of the article, we outline the challenges which hamper progress in research and extrapolate to developing and promising directions including additive manufacturing and synthetic biology that could benefit from molecular level understanding of interactions occurring between inanimate (abiotic) and living (biotic) materials.

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.