Abstract
The understanding of the mechanisms involved in the interaction of proteins with inorganic surfaces is of major interest in both fundamental research and applications such as nanotechnology. However, despite intense research, the mechanisms and the structural determinants of protein/surface interactions are still unclear. We developed a strategy consisting in identifying, in a mixture of hundreds of soluble proteins, those proteins that are adsorbed on the surface and those that are not. If the two protein subsets are large enough, their statistical comparative analysis must reveal the physicochemical determinants relevant for adsorption versus non-adsorption. This methodology was tested with silica nanoparticles. We found that the adsorbed proteins contain a higher number of charged amino acids, particularly arginine, which is consistent with involvement of this basic amino acid in electrostatic interactions with silica. The analysis also identified a marked bias toward low aromatic amino acid content (phenylalanine, tryptophan, tyrosine and histidine) in adsorbed proteins. Structural analyses and molecular dynamics simulations of proteins from the two groups indicate that non-adsorbed proteins have twice as many π-π interactions and higher structural rigidity. The data are consistent with the notion that adsorption is correlated with the flexibility of the protein and with its ability to spread on the surface. Our findings led us to propose a refined model of protein adsorption.
Highlights
The adsorption of proteins on surfaces is a quasi-universal phenomenon of major physiological and toxicological significance
NP size and shape were characterized by transmission electron microscopy (TEM) images (Figure 2A and 2B) and small-angle neutron scattering (SANS) experiments (Figure 2C)
Based on this visual examination, we proposed to classify the proteins into 3 groups: the adsorbed proteins (APs), the non-adsorbed proteins (NAPs) and the proteins showing an intermediate behavior
Summary
The adsorption of proteins on surfaces is a quasi-universal phenomenon of major physiological and toxicological significance. The mechanisms and structural determinants of protein/surface interactions are still unclear [1]. A crude description would assume that the main determinants of protein adsorption are electrostatic interactions on charged surfaces, and hydrophobic interactions on hydrophobic surfaces. This scheme is perfectly functional for chromatographic techniques [2], but fails to explain the “nonspecific adsorption” of proteins that occurs, for example, on biosensors, implants, etc [3,4]. The important question is, rather than why a given protein is adsorbed, why should another protein not be adsorbed on a surface? The answer to this important question depends on the physical and chemical structure of the surfaces considered The important question is, rather than why a given protein is adsorbed, why should another protein not be adsorbed on a surface? In other words, is there a determinant of the relative sensitivity of proteins to nonspecific interactions? Obviously, the answer to this important question depends on the physical and chemical structure of the surfaces considered
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