Understanding and controlling protein adsorption is a prerequisite to controlling the interaction of nanomaterials with physiological systems. Here, we apply shotgun mass spectrometry to systematically examine how nanoparticle size and the surface density of poly(ethylene glycol) (PEG) influences protein adsorption from serum. We find that size and PEG density determine the relative and total adsorbed abundance of over 80 different proteins. Increasing PEG density and nanoparticle size decreases total protein adsorption, but does not eliminate it. We further show that by controlling the composition of the adsorbed protein layer, nanoparticle size and PEG density determine the efficiency and mechanism of cell uptake. At low PEG densities, cell uptake is efficient and driven by adsorbed serum proteins, while at high density it is inefficient and independent of adsorbed serum proteins. The results of this study establish guidelines for the rational design of nanomaterials with controlled protein adsorption and cell uptake.

Nanoparticle size and PEG grafting density control protein adsorption and cellular interactions in a physiological environment

243rd National Meeting (2012)

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